Research reveals that memories may not be stored in synapses

http://newsroom.ucla.edu/releases/lost-memories-might-be-able-to-be-restored-new-ucla-study-indicates

Lost memories might be able to be restored, new UCLA study indicates

Research reveals that memories may not be stored in synapses, as previously thought

Stuart Wolpert | December 19, 2014


New UCLA research indicates that lost memories can be restored. The findings offer some hope for patients in the early stages of Alzheimer’s disease.

For decades, most neuroscientists have believed that memories are stored at the synapses — the connections between brain cells, or neurons — which are destroyed by Alzheimer’s disease. The new study provides evidence contradicting the idea that long-term memory is stored at synapses.

“Long-term memory is not stored at the synapse,” said David Glanzman, a senior author of the study, and a UCLA professor of integrative biology and physiology and of neurobiology. “That’s a radical idea, but that’s where the evidence leads. The nervous system appears to be able to regenerate lost synaptic connections. If you can restore the synaptic connections, the memory will come back. It won’t be easy, but I believe it’s possible.”

The findings were published recently in eLife, a highly regarded open-access online science journal.

Glanzman’s research team studies a type of marine snail called Aplysia to understand the animal’s learning and memory. The Aplysia displays a defensive response to protect its gill from potential harm, and the researchers are especially interested in its withdrawal reflex and the sensory and motor neurons that produce it.

They enhanced the snail’s withdrawal reflex by giving it several mild electrical shocks on its tail. The enhancement lasts for days after a series of electrical shocks, which indicates the snail’s long-term memory. Glanzman explained that the shock causes the hormone serotonin to be released in the snail’s central nervous system.

Long-term memory is a function of the growth of new synaptic connections caused by the serotonin, said Glanzman, a member of UCLA’s Brain Research Institute. As long-term memories are formed, the brain creates new proteins that are involved in making new synapses. If that process is disrupted — for example by a concussion or other injury — the proteins may not be synthesized and long-term memories cannot form.  (This is why people cannot remember what happened moments before a concussion.)

“If you train an animal on a task, inhibit its ability to produce proteins immediately after training, and then test it 24 hours later, the animal doesn’t remember the training,” Glanzman said.  “However, if you train an animal, wait 24 hours, and then inject a protein synthesis inhibitor in its brain, the animal shows perfectly good memory 24 hours later.  In other words, once memories are formed, if you temporarily disrupt protein synthesis, it doesn’t affect long-term memory. That’s true in the Aplysia and in human’s brains.”  (This explains why people’s older memories typically survive following a concussion.)

Glanzman’s team found the same mechanism held true when studying the snail’s neurons in a Petri dish. The researchers placed the sensory and motor neurons that mediate the snail’s withdrawal reflex in a Petri dish, where the neurons re-formed the synaptic connections that existed when the neurons were inside the snail’s body.  When serotonin was added to the dish, new synaptic connections formed between the sensory and motor neurons.  But if the addition of serotonin was immediately followed by the addition of a substance that inhibits protein synthesis, the new synaptic growth was blocked; long-term memory could not be formed.

The researchers also wanted to understand whether synapses disappeared when memories did. To find out, they counted the number of synapses in the dish and then, 24 hours later, added a protein synthesis inhibitor. One day later, they re-counted the synapses.

What they found was that new synapses had grown and the synaptic connections between the neurons had been strengthened; late treatment with the protein synthesis inhibitor did not disrupt the long-term memory. The phenomenon is extremely similar to what happens in the snail’s nervous system during this type of simple learning, Glanzman said.

Just to add this article.  The research around this molecule has a lot to do with mental perceptions and how the brain interacts with the wider world. I bet this is critical to Charge Field reception in the brain as well:

http://en.wikipedia.org/wiki/Serotonin

Molecular Formula: C₁₀H₁₂N₂O

http://www.chemspider.com/Molecular-Formula/C10H12N2O


I figure that the 5-HT receptors with serotonin are likely connected to particular charge field sensitivity-streams. Just a thought. Our "reality" is fully dependent on this molecule and these receptors:
 
http://en.wikipedia.org/wiki/5-HT_receptor

Just wanted to post this on Ligands (think of this in terms of Miles Mathis' 'bonding' with the Charge Field):

http://en.wikipedia.org/wiki/Ligand_%28biochemistry%29
-------

In biochemistry and pharmacology, a ligand is a substance (usually a small molecule) that forms a complex with a biomolecule to serve a biological purpose. In protein-ligand binding, the ligand is usually a signal-triggering molecule, binding to a site on a target protein. In DNA-ligand binding studies, the ligand is usually any small molecule or ion,^[1] or even a protein ^[2] that binds to the DNA double helix.

The binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and van der Waals forces. The docking (association) is usually reversible (dissociation). Actual irreversible covalent bonding between a ligand and its target molecule is rare in biological systems. In contrast to the meaning in metalorganic and inorganic chemistry, it is irrelevant whether the ligand actually binds at a metal site, as is the case in hemoglobin.

Ligand binding to a receptor (receptor protein) alters its chemical conformation (three-dimensional shape). The conformational state of a receptor protein determines its functional state. Ligands include substrates, inhibitors, activators, and neurotransmitters. The tendency or strength of binding is called affinity. Binding affinity is determined not only by direct interactions, but also by solvent effects that can play a dominant indirect role in driving non-covalent binding in solution.^[3]


Radioligands are radioisotope labeled compounds are used in vivo as tracers in PET studies and for in vitro binding studies.

Brain Networks Strengthened By Closing Ion Channels, Research Could Lead To ADHD Treatment

Date:
April 23, 2007
Source:
Yale University

Yale School of Medicine and University of Crete School of Medicine researchers report in Cell April 20 the first evidence of a molecular mechanism that dynamically alters the strength of higher brain network connections.

This discovery may help the development of drug therapies for the cognitive deficits of normal aging, and for cognitive changes in schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder (ADHD).

"Our data reveal how the brain's arousal systems influence the cognitive networks that subserve working memory-which plays a key role in abstract thinking, planning, and organizing, as well as suppressing attention to distracting stimuli," said Amy Arnsten, lead author and neurobiology professor at Yale.

The brain's prefrontal cortex (PFC) normally is responsible for so-called executive functions. The ability of the PFC to maintain such memory-based functions declines with normal aging, is weakened in people with ADHD, and is severely disrupted in disorders such as schizophrenia and bipolar disorder.

The current study found that brain cells in PFC contain ion channels called hyperpolarization-activated cyclic nucleotide-gated channels (HCN) that reside on dendritic spines, the tiny protrusions on neurons that are specialized for receiving information. These channels can open when they are exposed to cAMP (cyclic adenosine monophosphate). When open, the information can no longer flow into the cell, and thus the network is effectively disconnected. Arnsten said inhibiting cAMP closes the channels and allows the network to reconnect.

The study also found alpha-2A adrenergic receptors near the channels that inhibit the production of cAMP and allow the information to pass through into the cell, connecting the network. These receptors are stimulated by a natural brain chemical norepinephrine or by medications like guanfacine.

"Guanfacine can strengthen the connectivity of these networks by keeping these channels closed, thus improving working memory and reducing distractibility," she said. "This is the first time we have observed the mechanism of action of a psychotropic medication in such depth, at the level of ion channels."

Arnsten said the excessive opening of HCN channels might underlie many lapses in higher cognitive function. Stress, for example, appears to flood PFC neurons with cAMP, which opens HCN channels, temporarily disconnects networks, and impairs higher cognitive abilities.

There is also evidence that this pathway may not be properly regulated with advancing age, resulting in destruction of cAMP. The dysregulation of the pathway may contribute to increased forgetfulness and susceptibility to distraction as we grow older.

The research is also relevant to common disorders such as ADHD, which is associated with weaker regulation of attention and behavior. ADHD is highly heritable, and some patients with ADHD may have genetic changes in molecules that weaken the production of norepinephrine. Treatments for ADHD all enhance stimulation of the norepinephrine receptors.

These new data also have important implications for the researchers' studies of more severe mental illnesses like schizophrenia and bipolar disorder, which can involve mutations of a molecule called DISC1 (Disrupted in Schizophrenia) that normally regulates cAMP. Loss of function of DISC1 in patients with schizophrenia or bipolar disorder would increase vulnerability to cortical network disconnection and profound PFC deficits. This may be especially problematic during exposure to even mild stress, which may explain the frequent worsening of symptoms following exposure to stress. "We find it remarkable to relate a genetic mutation in patients to the regulation by an ion channel of PFC neuronal networks," said Arnsten.

Co-authors include Min Wang, Brian Ramos, Yousheng Shu, Arthur Simen, Alvaro Duqye, Avis Brennan, Susheel Vijayraghavan, Anne Dudley, Eric Nou, David McCormick, James Mazer and Constantinos Paspalas, who also has an appointment at the University of Crete School of Medicine in Heraklion, Greece.

The work was supported by research grants from the National Institute on Aging and the National Institute of Mental Health, as well as from Shire Pharmaceuticals Group plc and an award from the Kavli Institute of Neuroscience at Yale.

Arnsten and Yale have a license agreement with Shire Pharmaceuticals for the development of guanfacine for the treatment of patients with ADHD. Yale has submitted a patent application on the use of HCN blockers for the treatment of PFC cognitive deficits based on the data reported in the Cell paper.

Cell 129: 1-14 (April 20, 2007)
-------------------
cAMP
https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate

http://www.sciencedaily.com/releases/2007/04/070420143324.htm

Brain proteins apparently provide memory. How these proteins "release" the charge field to "fuel a memory" is key:
-------
https://en.wikipedia.org/wiki/Protein_synthesis_inhibitor

http://www.nbcnews.com/id/33191472/ns/health-alzheimers_disease/t/can-you-catch-alzheimers-disease/
(This has been increasing a lot over the last 15 years as US Baby-boomers have aged.)

For years, physicians and Alzheimer's experts have said that the earliest symptoms of the disease typically don't appear until you're in your 60s, 70s, or beyond. But now there's reason to believe that the first warning signs may actually crop up much earlier than that, and in a seemingly much more benign way: as cold sores, those embarrassing blisters that can erupt on the lips of people who are sick or run-down.

The sores are triggered by the herpes virus — most often, herpes simplex virus type 1 (not to be confused with HSV-2, which predominately causes genital herpes). In recent years, a growing body of research, much of it championed by a British scientist, has begun to suggest a startling fact: The same virus known for sabotaging people's social lives could be responsible for the majority of Alzheimer's cases.

"There's clearly a very strong connection," says the researcher, Ruth Itzhaki, Ph.D., speaking one afternoon in her office at the University of Manchester, in northwestern England. A neurobiologist, Itzhaki has spent the better part of two decades studying the link between herpes and Alzheimer's. "I estimate that about 60 percent of Alzheimer's cases could be caused by the virus."

...
What effect does the virus have when it reaches your brain? The short answer: That depends. In certain people it seems to do much less damage than in others; just as some of us never develop cold sores, some of us can have the herpes virus inside our brains without any horribly ill effects. But Itzhaki believes that in other people — specifically those who carry APOE e4, a gene form, or allele, strongly linked to Alzheimer's — the virus is not only reactivated by triggers like stress or a weakened immune system, but also actually begins to create the proteins that form the plaques and tangles presumed to be responsible for Alzheimer's.

---
Alzheimer’s disease linked to common viruses

Posted by: Abby Campbell, staff writer in Natural Healing September 4, 2015 4 Comments
While everyone has misplaced keys from time to time, this type of forgetfulness is normal. On the other hand, forgetting your child’s name or how to tie your shoe is a serious neurological problem called “Alzheimer’s disease.” While it is the most common form of dementia, it also has the most potential for damaging the brain’s neurons. Changes in the affected person include memory loss, the ability to think clearly, as well as odd behavior.

In previous years, Alzheimer’s was considered a chronic disease that resulted from cause and effect that included lifestyle factors. However, new research has proven an association with infectious disease. In fact, studies are showing up to 95 percent of the American population has been infected by a disease that could eventually result in Alzheimer’s.

There is a clear and present danger for all Alzheimer’s disease patients

Cytomegalovirus (CMV) is one of the causes of “the kissing disease” – better termed mononucleosis. While the symptoms of mononucleosis subside after a few weeks or months, CMV silently contributes to Alzheimer’s disease according to The Journal of Infectious Diseases.

In a human controlled study, CMV antibody levels showed a significantly higher association with neurofibrillary tangles which are commonly known as the primary markers for the disease. According to the Centers for Disease Control, CMV is in a person’s body for life once is it contracted. Among every 100 adults in the United States, 50 to 80 percent are infected by the age of 40.

http://www.naturalhealth365.com/alzheimers-disease-dementia-viruses-1550.html
---

Interesting that Herpes Simplex 1 virus shuts off various cell protein synthesis as well.

http://jvi.asm.org/content/78/3/1063.full
---
GENERAL FEATURES OF HSV-INDUCED HOST SHUTOFF: CONTEXT OF vhs ACTION

HSV infection leads to essentially complete suppression of cellular protein synthesis. This global shutoff stems from at least two distinct inhibitory pathways. First, the levels of most host mRNAs undergo a precipitous decline (12, 26), curtailing synthesis of the corresponding proteins. vhs contributes to this decline by globally increasing the rate of mRNA degradation in the cytoplasm (26, 63). The effect of vhs is magnified by virus-induced suppression of host mRNA synthesis, mediated through repression of primary transcription (59) and pre-mRNA splicing (16). As described below, the multifunctional IE protein ICP27 plays a particularly prominent role in the inhibition of host mRNA biogenesis at both of these levels. ICP27 thus collaborates with vhs to reduce the abundance of host mRNA during infection (15, 57). Second, HSV alters the function of the host translational apparatus, such that translation of the residual portion of many of the down-regulated cellular mRNAs is strongly impaired (14, 27). This effect is probably due to impaired initiation, as a significant fraction of the residual mRNAs is found in 48S translational preinitiation complexes (27). Little is known of the mechanisms underlying this translational control. However, vhs is apparently not involved (27) and this topic will not be considered further in this minireview.

Chapter 13
The strategy of herpes simplex virus replication and takeover of the host cell

Bernard Roizman and Brunella Taddeo.
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, USA

Gene content, organization, and fundamental design of the viral genome

Several aspects of the structure, content and function of the viral genome are worthy of note. They are as follows.

(ⅰ) We do not know with any degree of certainty the exact number of transcriptional units or proteins encoded by the viral genome. The problem stems from several considerations. The initial enumeration of open reading frames (ORFs) excluded sequences that lacked a TATA box, a canonical methionine intiation codon, a suitable length, or that situated antisense to a known or readily demonstrable ORF. The current list of HSV sequences that are expressed (see section on gene content) includes RNAs that do not appear to encode proteins (e.g., OriS RNAs), TATA-less ORFs (e.g., γ134.5), and ORFs that are antisense to each other (e.g., ORF P and ORF O vs. γ134.5, UL43.5 vs. UL43, UL27.5 vs. UL27, UL9.5 vs. UL10).

(ⅱ) Viral proteins can express multiple functions. The order of expression of these functions may be regulated by post-translational modification of the proteins or by interacting proteins present within various compartments of the cell. For example, the interaction of ICP22 with cellular proteins is determined by the status of post-translational phosphorylation by viral kinases (Leopardi et al., 1997b; Purves and Roizman, 1992; Purves et al., 1993). Post-translational modification of ICP0 is also required for its ubiquitin-ligase activities (Boutell et al., 2002; Hagglund et al., 2002) but is not necessary for other functions required for optimal replication of the virus such as its interactions with CoREST (Gu et al., 2005).

A powerful mechanism for regulation of specific functions encoded in a single protein is the synthesis from an independent transcriptional unit of a truncated protein whose sequence is colinear with the carboxyl-terminal domain of the larger protein. The functions encoded by the truncated proteins could enhance (e.g., US1.5 vs. α22) (Carter and Roizman, 1996; Purves et al., 1993) or inhibit (UL8.5 vs. UL9) (Baradaran et al., 1994) the function of the larger protein.

(ⅲ) There is little doubt that herpes simplex virions contain at least three proteins (US11, UL47 and UL49) that bind RNA from the infected cell and translocate it into the newly infected cell (Roller and Roizman, 1990; Sciortino et al., 2002). Evidence has been reported that this RNA can be expressed (Sciortino et al., 2002). A central issue is the impact of this RNA on the outcome of infection. A fundamental unanswered question is why HSV would carry RNA rather than more tegument proteins. One argument presented by Shenk (2002) is that proteins destined to membranes or secretory pathway would have to be made de novo and cannot be brought as components of the tegument.

https://www.ncbi.nlm.nih.gov/books/NBK47362/

Herbalist and former doctor, James Sloane, says a number of herbs are good at eradicating various viruses, such as Pau d'Arco, chaparral, etc, which can even cure cancer and HIV etc.

See https://www.google.com/search?q=site%3Acurezone.com+%22truth+in+medicine%22+virus&ie=utf-8&oe=utf-8

Alzheimers appears to be related to the regulation of Ferritin:

http://articles.mercola.com/sites/articles/archive/2012/07/19/excess-iron-leads-to-alzheimers.aspx

https://en.wikipedia.org/wiki/Ferritin

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

   NeurologyPhysical Medicine and Rehabilitation

Research output: Contribution to journal › Article

Abstract

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.

https://www.scholars.northwestern.edu/en/publications/ferritin-levels-in-the-cerebrospinal-fluid-predict-alzheimers-dis

Blood transferrin and ferritin in Alzheimer's disease
P. Fischer. Author links open the author workspace.1. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceM.E. Götz. Author links open the author workspace.2. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceW. Danielczyk. Author links open the author workspace.3. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceW. Gsell. Author links open the author workspace.2. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceP. Riederer. Author links open the author workspace.2. Numbers and letters correspond to the affiliation list. Click to expose these in author workspace

https://doi.org/10.1016/S0024-3205(97)00282-8

Abstract

In the present study we found a significant correlation between severity of dementia of Alzheimer's type (DAT) and both transferrin and ferritin serum levels. Levels of transferrin in serum of 41 DAT patients tended to be lower than those of 19 age-matched controls, while levels of ferritin were not significantly different in DAT patients compared to controls. These results are interpreted in line with previous findings of higher brain ferritin and lower brain transferrin levels in DAT and are a circumstantial support for the oxygen radical hypothesis of degenerative brain disease.

http://www.webmd.com/alzheimers/news/20000228/high-iron-levels-identified-in-brains-of-alzheimers-patients#1

UCLA study suggests iron is at core of Alzheimer's disease
Findings challenge conventional thinking about possible causes of disorder
Mark Wheeler | August 20, 2013
http://newsroom.ucla.edu/releases/ucla-study-suggests-that-iron-247864

Massive Ferritin Elevation in Neonatal Herpes Simplex Virus Infection: Hemophagocytic Lymphohistiocytosis or Herpes Simplex Virus Alone?

Published: 20 February 2015

Neonatal herpes simplex virus [HSV] infection remains a common problem worldwide, affecting up to 1 of 3000 live births in the United States. Approximately 25% of infants infected with HSV develop disseminated disease [ 1 ]. Although the exact mechanisms are unclear, disseminated HSV infection has been reported as a trigger of neonatal hemophagocytic lymphohistiocytosis (HLH) [ 2 ]. A hallmark feature of this complex syndrome is a highly elevated ferritin level, with 1 recent report suggesting that a ferritin level of more than 10 000 μg/L was 96% specific for HLH [ 3 ]. We report 3 recent cases at our institution in which ferritin levels were very elevated in the setting of disseminated neonatal HSV disease. Although the diagnosis of HLH was considered, these cases call into question the specificity of ferritin >10 000 μg/L as a diagnostic marker for HLH and raise the possibility that this degree of hyperferritinemia may be related to the inflammatory effects of disseminated HSV infection alone. This conclusion, if sustained by further research, carries significant therapeutic implications given the risks of immunosuppressive therapy in the setting of concomitant disseminated infection.

https://academic.oup.com/jpids/article/4/3/e48/2580155/Massive-Ferritin-Elevation-in-Neonatal-Herpes

------

Herpes and Cold Sore Outbreaks

Painful herpes blisters and cold sores are caused by the herpes simplex virus (HSV-2 and HSV-1). There is no cure for the herpes simplex virus. Conventional topical and oral treatments are widely available and can treat herpes and cold sores with various degrees of success. But why do some people get mild occasional outbreaks while others suffer from more severe and frequently recurring outbreaks? Why do some people with the virus get no outbreaks at all?

Iron’s relationship to the herpes simplex virus

A 1995 study in the “European Journal of Clinical Microbiology and Infectious Diseases” looks at the impact of ferritin levels (iron stores) on recurring herpes simplex outbreaks compared patients with cold sores to those without cold sores and found that patients with cold sores had lower ferritin levels.
A 2010 medical study in the journal “Cell Biochemistry and Function” suggests that the reason why some people get cold sores and others do not can be partly explained by genetic differences in the way our bodies handle iron. This is due to differences in the protein haptoglobin which is important to iron metabolism. There are three types of haptoglobin two of which lead to lower levels of iron in the blood. People with one of these two kinds of haptoglobin are more likely to get herpes outbreaks.

How iron prevents herpes outbreaks

In order to infect new cells and cause an outbreak, the herpes virus needs an enzyme called ribonucleotide reductase. Iron is an essential component of this enzyme.  Our immune system (T-cells and B-cells) also relies on iron to fight the herpes simplex virus. Unfortunately, the herpes simplex virus binds iron more effectively than our immune system so when iron stores (ferritin levels) are low, the virus wins out, and we get herpes and cold sore outbreaks.
Iron treatment for herpes

Iron treatment for herpes is simple and straight forward: take iron to improve your ferritin levels. Because it can be dangerous to take iron when you don’t need it, we urge you to get a blood test to determine your ferritin levels and take advice from a health practitioner about how much and what kind of iron you should take to improve your ferritin levels.

-------

Gene Therapy 20, 589-596 (June 2013) | doi:10.1038/gt.2012.70

Quantification of HSV-1-mediated expression of the ferritin MRI reporter in the mouse brain

B Iordanova, W F Goins, D S Clawson, T K Hitchens and E T Ahrens
Abstract

The development of effective strategies for gene therapy has been hampered by difficulties verifying transgene delivery in vivo and quantifying gene expression non-invasively. Magnetic resonance imaging (MRI) offers high spatial resolution and three-dimensional views, without tissue depth limitations. The iron-storage protein ferritin is a prototype MRI gene reporter. Ferritin forms a paramagnetic ferrihydrite core that can be detected by MRI via its effect on the local magnetic field experienced by water protons. In an effort to better characterize the ferritin reporter for central nervous system applications, we expressed ferritin in the mouse brain in vivo using a neurotropic herpes simplex virus type 1 (HSV-1). We computed three-dimensional maps of MRI transverse relaxation rates in the mouse brain with ascending doses of ferritin-expressing HSV-1. We established that the transverse relaxation rates correlate significantly to the number of inoculated infectious particles. Our results are potentially useful for quantitatively assessing limitations of ferritin reporters for gene therapy applications.

http://www.nature.com/gt/journal/v20/n6/full/gt201270a.html

------

Pretty good coverage of Ferritin in vivo:

Ferritin: At the Crossroads of Iron and Oxygen Metabolism12

Elizabeth C. Theil
http://jn.nutrition.org/content/133/5/1549S.full

----------

Ferritin proteins yield ultrathin computer memory
28 Sep 2007

Ferritin and Detective Conan --

Researchers from the Nara Institute of Science and Technology have developed a biotech-based process for creating ultrathin computer memory. The process, which uses a protein commonly found in mammals, allows memory to be built on thinner substrates because it eliminates the need for high-temperature processing, and it could lead to significantly smaller and thinner computers in the near future, suggest the researchers.

Computer memory typically consists of millions of circuit elements, known as memory cells, which are made of metal and arranged on a silicon substrate. Because the manufacturing process involves temperatures in excess of 1,000 degrees Celsius (1,832 degrees Fahrenheit), the substrate must have a high heat resistance, making thin materials with low heat resistance, such as glass and plastics, unsuitable. However, by using ferritin -- a globular protein complex that stores iron inside its hollow spherical structure, and which is commonly found in the bodies of mammals -- the research group developed a way to arrange metal memory cells on substrates without heat, allowing for the use of thinner substrate materials.

In this new method, ferritin containing metal molecules is applied to a substrate and allowed to self-assemble into a high-density, ordered arrangement. The ferritin is then irradiated with UV light, which completely destroys the protein and leaves behind tiny metal deposits on the substrate. In this way, the researchers bypassed the need for high-temperature processing, allowing for the creation of ultrathin memory chips that measure less than 1 micron in thickness.

The researchers, who happen to be fans of the popular Detective Conan (a.k.a. "Case Closed") series of manga and anime, say their success marks a major step forward in the development of ultrathin computers that, if coupled with ultrathin displays, could one day be used in devices like the high-tech eyeglasses that appear in Detective Conan. The Detective Conan series, which is authored by Gosho Aoyama, centers around Shin'ichi Kudo ("Jimmy Kudo" in the US version), a young detective that has been transformed into a prepubescent boy who goes by the alias of Edogawa Conan and who is armed with an array of high-tech gadgets like computerized eyeglasses, a voice-changing bow tie, and power-boost sneakers.

Research team leader and electronics engineering professor Yukiharu Uraoka says, "We are well on the way to developing computers built on thin films that can be integrated into eyeglass lenses or into clothing. Conan's eyeglasses are no longer a dream."

In response to the development, Gosho Aoyama, Conan's creator, says, "It is a great thrill to see an idea on the pages of a manga become a reality. Next, if possible, I'd like someone to develop power-boost sneakers."

http://pinktentacle.com/2007/09/ferritin-proteins-yield-ultrathin-computer-memory/

Keep in mind future nano-super conducting chips... my best guess at this time is that "memory" is stored and recall connected to bio-ferritin?

Just to add this. Brain Insulin regulates Iron function in the brain as well.

http://www.alz.org/mnnd/documents/breakout_session_310.pdf

Intranasal Insulin Improves Memory in Patients with Alzheimer's Disease


The Blind Researchers and Alzheimer’s Disease
Tangles
Amyloid
Iron
Acetylcholine
Insulin Glutamate

I.N. Deferoxamine Protects Against AD & Stroke

Iron is elevated in the brains of patients
with AD, stroke, Parkinson’s other brain disorders. This is not because we ingest
too much iron, but rather because our brains do not handle the
iron properly.

Deferoxamine (DFO), developed in the 1960s, binds iron very
tightly and can help remove it from the body.

Intranasal DFO reduces brain damage in rats by 55% even when
a stroke occurs two days after treatment. DFO preconditions the
brain to protect it against damage.

Intranasal DFO reduces memory loss in a mouse model of AD
and improves memory in normal mice.

Intramuscular DFO
cut the rate of functional decline in AD
patients by 50% over two years. Intranasal DFO should be more
effective and avoid systemic side effects

http://www.alz.org/mnnd/documents/breakout_session_310.pdf

How does brain insulin resistance develop in Alzheimer's disease?
Fernanda G. De Felice. Author links open the author workspace.Opens the author workspaceOpens the author workspaceMychael V. Lourenco. Author links open the author workspace.Sergio T. Ferreira

Abstract

Compelling preclinical and clinical evidence supports a pathophysiological connection between Alzheimer's disease (AD) and diabetes. Altered metabolism, inflammation, and insulin resistance are key pathological features of both diseases. For many years, it was generally considered that the brain was insensitive to insulin, but it is now accepted that this hormone has central neuromodulatory functions, including roles in learning and memory, that are impaired in AD. However, until recently, the molecular mechanisms accounting for brain insulin resistance in AD have remained elusive. Here, we review recent evidence that sheds light on how brain insulin dysfunction is initiated at a molecular level and why abnormal insulin signaling culminates in synaptic failure and memory decline. We also discuss the cellular basis underlying the beneficial effects of stimulation of brain insulin signaling on cognition. Discoveries summarized here provide pathophysiological background for identification of novel molecular targets and for development of alternative therapeutic approaches in AD.

http://www.sciencedirect.com/science/article/pii/S155252601302918X

------

Brain insulin plays critical role in the development of diabetes

Date:
   February 16, 2011
Source:
   The Mount Sinai Hospital / Mount Sinai School of Medicine
Summary:
   Researchers have discovered a novel function of brain insulin, indicating that impaired brain insulin action may be the cause of the unrestrained lipolysis that initiates and worsens Type 2 diabetes in humans.

Furthermore, in mice that lacked the brain insulin receptor, lipolysis was unrestrained. While fatty acids are important energy sources during fasting, they can worsen diabetes, especially when they are released after the person has eaten, as happens in people with diabetes. Researchers previously believed that insulin's ability to suppress lipolysis was entirely mediated through insulin receptors expressed on adipocytes, or fat tissue cells.

"We knew that insulin has this fundamentally important ability of suppressing lipolysis, but the finding that this is mediated in a large part by the brain is surprising," said Dr. Buettner. "The major lipolysis-inducing pathway in our bodies is the sympathetic nervous system and here the studies showed that brain insulin reduces sympathetic nervous system activity in fat tissue. In patients who are obese or have diabetes, insulin fails to inhibit lipolysis and fatty acid levels are increased. The low-grade inflammation throughout the body's tissue that is commonly present in these conditions is believed to be mainly a consequence of these increased fatty acid levels."

Dr. Buettner added, "When brain insulin function is impaired, the release of fatty acids is increased. This induces inflammation, which can further worsen insulin resistance, the core defect in type 2 diabetes. Therefore, impaired brain insulin signaling can start a vicious cycle since inflammation can impair brain insulin signaling." This cycle is perpetuated and can lead to type 2 diabetes. Our research raises the possibility that enhancing brain insulin signaling could have therapeutic benefits with less danger of the major complication of insulin therapy, which is hypoglycemia."

Dr. Buettner's team plans to further study conditions that lead to diabetes such as overfeeding to test if excessive caloric intake impairs brain insulin function. A major second goal will be to find ways of improving brain insulin function that could break the vicious cycle by restraining lipolysis and improving insulin resistance. This study is supported by a grant from the National Institutes of Health and the American Diabetes Association. First author of the study is Thomas Scherer, PhD, postdoctoral fellow in the Department of Medicine in the Division of Endocrinology, Diabetes and Bone Disease.

----
Ketones to combat Alzheimer’s disease
Posted July 16, 2016
These promising early findings of ketogenic compounds offered hope that dietary interventions might similarly benefit brain health. A 2012 study tested whether memory could be improved simply by adopting a low-carbohydrate diet, without the need of supplements used in the prior studies. Of 23 individuals with MCI, those following a very low-carbohydrate diet for six weeks showed improved memory compared to those on a high-carbohydrate diet. These memory improvements correlated with ketone levels, but not with calories consumed, insulin levels or body weight, pointing to increased ketogenesis as the likely reason for the low-carb dieters’ cognitive enhancement.

Other potential AD treatments have similarly shown short-term therapeutic effects in early disease stages but have flopped when put to the test in more advanced, long-term cases. Although ketosis hasn’t been rigorously tested in a formal clinical trial, a recent case study provides compelling evidence that ketones might in fact hold up in severe clinical cases. A 63 year-old man with advanced AD began consuming coconut oil and medium chain triglycerides, both known to increase ketone levels. After just 2.5 months, his score on the Mini Mental State Exam, a test of global cognitive function, increased from an extremely low 12 to 20 (out of a max 30). After two years, his cognitive ability and daily living functions both improved and his MRI showed no further brain atrophy. After adding a ketone ester supplement to his dietary regimen, the patient showed even further improvements in his mood, self-sufficiency and memory. Notably, this man carried the ApoE4 gene; thus, ketosis does appear to be highly beneficial for ApoE4 carriers, even if prior studies indicate it’s even more helpful for those without this risk factor.

How ketones protect the brain

Researchers have looked to animal models to better understand how ketosis might protect the human brain from neurodegeneration. In a mouse model of AD, levels of beta-amyloid, a toxic protein that is elevated in AD, were reduced in the brains of mice fed a high-fat/low-carb diet compared to those on a standard diet. A more recent study helped to clarify the link between the metabolic benefits of ketones, lower amyloid and improved cognitive function. This study tested the effects ketones both in a mouse model of AD and in neurons treated with amyloid. While amyloid increased oxidation and disrupted function of a mitochondrial enzyme complex, ketones reversed these effects, confirming their neural metabolic benefits. Furthermore, ketones reduced amyloid levels and blocked the formation of pores in cell membranes induced by amyloid, showing that ketones can protect against neuronal damage related to amyloid. Finally, ketones restored normal synaptic plasticity and memory performance that were impaired by amyloid.

http://blogs.plos.org/neuro/2016/07/16/ketones-to-combat-alzheimers-disease/

Some more recent news on Alzheimer's and Olive oil:
---
Extra-virgin olive oil prevents dementia by prompting the brain to clear out harmful debris, reveal scientists as they hail 'exciting' breakthrough

   Oil is a key ingredient of a Mediterranean diet, which has many health benefits
   Study found olive oil prompts the brain to remove harmful clutter in the brain
   Olive oil reduces the amount of amyloid-beta plaques and neurofibrillary tangles
   These structures increase a person's likelihood of getting Alzheimer's disease

By Daisy Dunne For Mailonline

Published: 13:30 BST, 21 June 2017 | Updated: 21:57 BST, 21 June 2017

Lead researcher Professor Domenico Pratico, from Temple University in Pennsylvania, said: 'We found that olive oil reduces brain inflammation but most importantly activates a process known as autophagy.'

Autophagy is the process by which cells break down and clear out unwanted debris left in the body.

Mice with induced Alzheimer's who were fed a diet of olive oil had higher levels of autophagy in the brain, according to researchers.

Professor Pratico said: 'Brain cells from mice fed diets enriched with extra-virgin olive oil had higher levels of autophagy and reduced levels of amyloid plaques and phosphorylated tau.'

Oil is a staple of the Mediterranean diet, which is associated with a variety of health benefits

Phosphorylated tau is responsible for neurofibrillary tangles, which are suspected of contributing to the poor memory of Alzheimer's patients.

Previous research has suggested that the widespread use of extra-virgin olive oil in the Mediterranean diet is key to its health benefits.

Professor Pratico said: 'The thinking is that extra-virgin olive oil is better than fruits and vegetables alone, and as a monounsaturated vegetable fat it is healthier than saturated animal fats.'

http://www.dailymail.co.uk/health/article-4625116/Extra-virgin-olive-oil-prevents-dementia-memory-loss.html

----
Coconut oil is derived from the milk in coconuts and consists of coconut fat and lauric acid, a fatty acid that is transformed into monolaurin.


...
Monolaurin is a nontoxic, antiviral supplement made from lauric acid (a fatty acid found in breast milk) and glycerin. It is used to treat infections with all strains of the herpes virus along with other viral infections including measles, and HIV, the human immunodeficiency virus that causes AIDS. Monolaurin is believed to have the potential to permanently inactivate the fat coated viruses that cause these diseases by fluidizing the lipids (fats) and phospholipids in their envelopes, leading to the disintegration of viral particles.

Monolaurin, sold under the brand name Lauricidin®, comes in the form of mini pellets. Dosage must be individualized. Jon J. Kabara, MD, the physician/researcher who developed monolaurin, says that the usual recommended initial dose is 1.5 grams once or twice a day for one or two weeks. The dose can be increased to 3.0 grams once or twice daily thereafter. A maintenance dose can be 3.0 grams two or three times a day. The idea is to start with a low dose and then increase it gradually until you notice a positive response.

I feel strongly that you take monolaurin only under the supervision of your physician who can order monolaurin for you, determine your best dosage and monitor your progress. However, Dr. Kabara has generously offered to respond to individual questions about dosage submitted with orders via his Web site, www.lauricidin.com.

https://www.drweil.com/health-wellness/body-mind-spirit/sexual-health/halting-herpes/

---------

http://www.dailymail.co.uk/health/article-2258665/Alzeimers-Can-coconut-oil-ease-Families-whove-given-loved-ones-swear-it.html

Can coconut oil ease Alzheimer's? Families who've given it to loved ones swear by it

By Jerome Burne for MailOnline

Published: 00:05 BST, 8 January 2013 | Updated: 15:20 BST, 14 January 2013
THE TROUBLE WITH DEMENTIA DRUGS

These stories, however, do suggest pure coconut oil — and the MCT oil that can be extracted from it — is worth investigating.

Currently, the only type of drug available for Alzheimer’s patients, known as a cholinesterase inhibitor, works by boosting the amount of a brain chemical they are lacking.

It slows memory decline in about a third of patients for between six months and a year.
Currently, the only type of drug available for Alzheimer's patients works by boosting the amount of a brain chemical they are lacking

Currently, the only type of drug available for Alzheimer's patients works by boosting the amount of a brain chemical they are lacking

Last year, the NHS spent more than £70 million on the most widely used brand, Aricept. Its potential side-effects include nausea, diarrhoea and slow heart rhythms, which can lead to fainting.

Hundreds of millions of pounds have been spent trying to develop drugs to clear the plaques of damaged protein in the brain that are the classic sign of Alzheimer’s, but all have failed to get a licence.

So could tackling the energy supply to the brain be another option?

One expert who thinks it’s worth investigating is Professor Rudy Tanzi, director of the Genetics and Ageing Research Unit at Massachusetts General Hospital and professor of neurology at Harvard Medical School.

In a recent article for the Cure Alzheimer’s Fund, he explained why coconut oil might work.

‘Virgin coconut oil contains the fats that can be converted into ketone bodies, which can serve as an alternate energy source for the brain.

'The ketone bodies could potentially provide energy to  the glucose-deprived brains of Alzheimer’s patients.’
ARE THERE ANY DRAWBACKS?

He stressed that, as yet, there was no evidence —– and warned that coconut oil itself has its own down-side.

‘The fats (found in coconut oil) can be potentially harmful to the heart, so it would be wise to regularly monitor cholesterol and triglyceride levels if you are taking it.’

Anyone interested in boosting their ketone supply in this way has three options — at least in the U.S.

As well as coconut oil there is MCT oil, which can be bought over the counter and has been used by some athletes for years (ketones also power muscles), and the patented food supplement drink that triggered Dr Newport’s original experiment.

The more expensive patented supplement is called Axona, and has a licence from the U.S. Food and Drug Administration for use as a medical food for patients with mild to moderate Alzheimer’s who are taking a drug such as Aricept. It’s not available in the UK.

‘The attraction of Axona for doctors is that it provides a well-studied, pure and concentrated dose of the ketone-producing properties found in coconut oil, while eliminating the multitude of triglyceride-elevating components it can contain,’ says Dr Richard S. Isaacson, associate professor of clinical neurology at the University of Miami Miller School of Medicine.

Food company Nestle recently bought a stake in the manufacturer, Acera, and is planning the sort of large, expensive clinical trial that, if successful, could get Axona a drug licence.

‘This would encourage more doctors to use it and insurance companies would pay for it — at the moment most don’t,’ says James Galvin, a professor of neurology and psychiatry at New York University.

Professor Galvin is the author of an article in the June edition of Neurodegenerative Disease Management that recommends taking Axona in combination with the Aricept-type drugs. (He, like Dr Isaacson, is a consultant for the manufacturer Acera).

‘It’s a rational approach that may result in maximum preservation of cognitive function,’ he says.

‘The ketone-boosting approach to Alzheimer’s seems to work in about half the patients. I’d recommend coconut oil as well if there was some good trial evidence for it.’

This evidence could soon be coming from the first coconut trial now being set up by Dave Morgan, professor of molecular pharmacology and physiology and head of the USF Health Byrd Alzheimer’s Institute in Florida.

‘I was very impressed by the anecdotal evidence gathered by Dr Newport,’ he says. ‘Patients want to know if it works and who is going to benefit, but our physicians have no scientific basis to advise them.

‘It will be a placebo-controlled trial on patients with mild to moderate Alzheimer’s. I don’t expect it to slow the progression of the disease, but it does seem to improve some of the symptoms.’

In the Scientific Discoveries section I just added a link to a new article on memories that says it's important to forget most things and there's a selection process for forgetting.

I dunno...but it sounds like a researcher's imagination running wild.

-------

more at link:
https://www.sciencedaily.com/releases/2017/06/170612094100.htm

'Multi-dimensional universe' in brain networks

Using mathematics in a novel way in neuroscience, scientists demonstrate that the brain operates on many dimensions, not just the 3 dimensions that we are accustomed to

Date:
   June 12, 2017
Source:
   Frontiers
Summary:
   Using a sophisticated type of mathematics in a way that it has never been used before in neuroscience, a scientists have uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain. This research has significant implications for our understanding of the brain.

For most people, it is a stretch of the imagination to understand the world in four dimensions but a new study has discovered structures in the brain with up to eleven dimensions -- ground-breaking work that is beginning to reveal the brain's deepest architectural secrets.

Using algebraic topology in a way that it has never been used before in neuroscience, a team from the Blue Brain Project has uncovered a universe of multi-dimensional geometrical structures and spaces within the networks of the brain.

The research, published today in Frontiers in Computational Neuroscience, shows that these structures arise when a group of neurons forms a clique: each neuron connects to every other neuron in the group in a very specific way that generates a precise geometric object. The more neurons there are in a clique, the higher the dimension of the geometric object.

"We found a world that we had never imagined," says neuroscientist Henry Markram, director of Blue Brain Project and professor at the EPFL in Lausanne, Switzerland, "there are tens of millions of these objects even in a small speck of the brain, up through seven dimensions. In some networks, we even found structures with up to eleven dimensions."

Markram suggests this may explain why it has been so hard to understand the brain. "The mathematics usually applied to study networks cannot detect the high-dimensional structures and spaces that we now see clearly."

If 4D worlds stretch our imagination, worlds with 5, 6 or more dimensions are too complex for most of us to comprehend. This is where algebraic topology comes in: a branch of mathematics that can describe systems with any number of dimensions. The mathematicians who brought algebraic topology to the study of brain networks in the Blue Brain Project were Kathryn Hess from EPFL and Ran Levi from Aberdeen University.

"Algebraic topology is like a telescope and microscope at the same time. It can zoom into networks to find hidden structures -- the trees in the forest -- and see the empty spaces -- the clearings -- all at the same time," explains Hess.

In 2015, Blue Brain published the first digital copy of a piece of the neocortex -- the most evolved part of the brain and the seat of our sensations, actions, and consciousness. In this latest research, using algebraic topology, multiple tests were performed on the virtual brain tissue to show that the multi-dimensional brain structures discovered could never be produced by chance. Experiments were then performed on real brain tissue in the Blue Brain's wet lab in Lausanne confirming that the earlier discoveries in the virtual tissue are biologically relevant and also suggesting that the brain constantly rewires during development to build a network with as many high-dimensional structures as possible.

When the researchers presented the virtual brain tissue with a stimulus, cliques of progressively higher dimensions assembled momentarily to enclose high-dimensional holes, that the researchers refer to as cavities. "The appearance of high-dimensional cavities when the brain is processing information means that the neurons in the network react to stimuli in an extremely organized manner," says Levi. "It is as if the brain reacts to a stimulus by building then razing a tower of multi-dimensional blocks, starting with rods (1D), then planks (2D), then cubes (3D), and then more complex geometries with 4D, 5D, etc. The progression of activity through the brain resembles a multi-dimensional sandcastle that materializes out of the sand and then disintegrates."

The big question these researchers are asking now is whether the intricacy of tasks we can perform depends on the complexity of the multi-dimensional "sandcastles" the brain can build. Neuroscience has also been struggling to find where the brain stores its memories. "They may be 'hiding' in high-dimensional cavities," Markram speculates.

Posted: Jul 23, 2018

Engineers model a graphene-based artificial synapse after the human brain

(Nanowerk News) Digital computation has rendered nearly all forms of analog computation obsolete since as far back as the 1950s. However, there is one major exception that rivals the computational power of the most advanced digital devices: the human brain.

The human brain is a dense network of neurons. Each neuron is connected to tens of thousands of others, and they use synapses to fire information back and forth constantly. With each exchange, the brain modulates these connections to create efficient pathways in direct response to the surrounding environment. Digital computers live in a world of ones and zeros. They perform tasks sequentially, following each step of their algorithms in a fixed order.
A team of researchers from Pitt's Swanson School of Engineering have developed an "artificial synapse" that does not process information like a digital computer but rather mimics the analog way the human brain completes tasks. Led by Feng Xiong, assistant professor of electrical and computer engineering, the researchers published their results in the recent issue of the journal Advanced Materials ("Low-Power, Electrochemically Tunable Graphene Synapses for Neuromorphic Computing").

Pitt engineers built a graphene-based artificial synapse in a two-dimensional, honeycomb configuration of carbon atoms that demonstrated excellent energy efficiency comparable to biological synapses. (Image: Swanson School of Engineering)

"The analog nature and massive parallelism of the brain are partly why humans can outperform even the most powerful computers when it comes to higher order cognitive functions such as voice recognition or pattern recognition in complex and varied data sets," explains Dr. Xiong.
An emerging field called "neuromorphic computing" focuses on the design of computational hardware inspired by the human brain. Dr. Xiong and his team built graphene-based artificial synapses in a two-dimensional honeycomb configuration of carbon atoms. Graphene's conductive properties allowed the researchers to finely tune its electrical conductance, which is the strength of the synaptic connection or the synaptic weight. The graphene synapse demonstrated excellent energy efficiency, just like biological synapses.
(more at link: https://www.nanowerk.com/nanotechnology-news2/newsid=50738.php )

---------------

This radio show is quite good on Memories and overall Brain function.


Episode 27 – Dr Adrian Owen
Does Brain Training Improve Mental Performance?


What You’ll Learn

The Cambridge Brain Sciences was set up to research and assess brain training tools (06:59).
Previously, brain function was researched by testing brain damaged participants (10:30).
In the 1990’s brain imaging techniques (PET scans and fMRIs) became important tools for brain assessment (11:40).
Dr. Owen explains further the definitions of fluid intelligence and crystalised intelligence (17:56).
Research using these brain training tasks, games, exercises, etc. usually focuses on fluid intelligence (20:22).
Dr. Owen describes further the brain-based tests used by Cambridge Brain Sciences (20:52).
Damien and Dr. Owen discuss the use of these cognitive tests to assess your own brain performance on a regular basis (22:43).
Cambridge Brain Sciences is hoping to encourage people to use their tools to assess whether brain training and interventions (such as coffee, etc.) can affect their own cognitive performance (25:12).
If you are going to run your own “experiments” to test the training or interventions, be your own scientist and carefully employ “good” research techniques (26:16).
Remember, what works for you may not always work for another (27:24).
Dr. Owen begins discussing “transfer” of training: to improve upon many aspects, not just the one (29:06).
The Cambridge Brain Sciences study also compared the lifestyles of the participants as related to their performance on the different tests analyzed in the study (36:18).
Damien and Dr. Owen discuss the damage that occurs to the brain from aging, injury, etc. and the fact that these cognitive declines are specific to each individual person (41:07).
Neuroplasticity is defined and discussed as a “change in the brain” following the learning process (45:04).
Dr. Owen discusses the use of EEG, a cheaper alternative, to analyze aspects such as consciousness that have previously been assessed with an fMRI, a more expensive machine (51:51).
Dr. Owen shares his thoughts for the future of cognitive performance including brain training and a short description of neuroenhancers, often called “smart drugs” (55:00).
Dr. Adrian Owen’s one biggest recommendation on using body data to improve your health, longevity and performance (1:00:10).

http://quantifiedbody.podbean.com/mf/web/kapu7w/Quantified-Body-Podcast-Ep-27-Benchmark-Cognitive-Performance-Brain-Training-with-Dr-Adrian-Owen.mp3

https://thequantifiedbody.net/brain-training-improve-mental-performance-dr-adrian-owen/

He needs to look at Miles' C.F. to get it working accurately.

Neuralink Corporation is an American neurotechnology company founded by Elon Musk and others, developing implantable brain–machine interfaces (BMIs). The company's headquarters are in San Francisco;[7] it was started in 2016 and was first publicly reported in March 2017.[1][2]

https://en.m.wikipedia.org/wiki/Neuralink
.......

Elon Musk's Neuralink Brain Chip Will Soon Allow Users to Take Charge of Moods and Emotions
By Isaiah Alonzo staff@techtimes.com | Aug 04, 2020 09:53 PM EDT

BOCA CHICA, TX - SEPTEMBER 28: SpaceX CEO Elon Musk gives an update on the next-generation Starship spacecraft at the company's Texas launch facility on September 28, 2019 in Boca Chica near Brownsville, Texas. The Starship spacecraft is a massive vehicle meant to take people to the Moon, Mars, and beyond. (Photo : (Photo by Loren Elliott/Getty Images))
Elon Musk's Neuralink currently develops a new feature on their brain chip that will enable humans to go forth and choose the mood by balancing off a person's hormone levels.

The secret project mentioned by Musk teased an update that will provide new feats for the company. He stated that an event on August 28, 2020, will thoroughly explain what the Tech CEO pertains.

The American Tech Company founded by Musk, Neuralink, is working on their current project, the brain-implanted chip, that is capable of controlling a human's emotion and mood by emitting waves that are beyond the usual or natural frequency and amplitude.

Neuralink pushes through updating the software of the project, as well as the chip and other hardware of the project. The Electronics reports that this software update aims to make the project more potent by programming its algorithms to learn more and improve the overall system. The Neuralink ASIC neural processor is upgraded as well, together with the project's proposed threads that are going to be used to collect data from the brain.

The brain chip's function would move forward from its original innovation of helping people with an entirely severed spinal cord to restore mobility and movement. The tech would help in alleviating stress and anxiety by altering and balancing the brain's hormone levels, relieving emotional tension.

The Neuralink Technology
Neuralink's promising technology makes use of flexible threads that are believing it to be safe and effective for a brain implant. This technology will cause less of the supposed or expected harm that befalls the implant on a person's brains.

The thread will function as it is named by having a device performing as a "sewing machine" that will then sew threads to the brain chip that can be connected via a USB-C cable to transmit vast loads of data for each person's intended use.

This technology is capable of connecting the human brain to a computer if it emerges successful and able to produce a working prototype. A chunk load of data bandwidth will be available for streaming and use for the human brain.

Musk is also optimistic for the chip to be parring with artificial intelligence as the project progresses. The company's team of scientists and researchers said in a published paper, last year.

https://www.techtimes.com/articles/251574/20200804/elon-musk-neuralink-update-mood-control.htm


In July 2019, Neuralink held a live-streamed presentation at the California Academy of Sciences. The proposed future technology involves a module placed outside the head that wirelessly receives information from thin flexible electrode threads embedded in the brain.[9] The system could include "as many as 3,072 electrodes per array distributed across 96 threads" each 4 to 6 μm in width.[9][20] The threads would be embedded by a robotic apparatus, with the intention to avoid damaging blood vessels.[9][21] Currently, electrodes are still too big to record the firing of individual neurons, so they can record only the firing of a group of neurons[citation needed]; Neuralink representatives believe this issue might get mitigated algorithmically, but it's computationally expensive and does not produce exact results.

https://en.m.wikipedia.org/wiki/Neuralink

Some research on Harmine and Herpes Simplex Viruses. The same elements are in play to fight Type-1 diabetes auto-immune attacks on the pancreas:
-----------
https://pubmed.ncbi.nlm.nih.gov/26348003/

Antiviral Res
. 2015 Nov;123:27-38. doi: 10.1016/j.antiviral.2015.09.003. Epub 2015 Sep 5.
Harmine blocks herpes simplex virus infection through downregulating cellular NF-κB and MAPK pathways induced by oxidative stress

Deyan Chen 1, Airong Su 1, Yuxuan Fu 1, Xiaohui Wang 1, Xiaowen Lv 1, Wentao Xu 1, Shijie Xu 1, Huanru Wang 1, Zhiwei Wu 2
Affiliations expand
PMID: 26348003 DOI: 10.1016/j.antiviral.2015.09.003

Abstract
Herpes simplex virus types 1 and 2 (HSV-1 and -2) are highly prevalent in many populations and therapeutic options are limited. Both viruses can establish latency by maintaining viral genomes in neurons of sensory ganglia. Primary or recurrent HSV infections may lead to deleterious outcomes: HSV-1 infection may result in corneal blindness and encephalitis and HSV-2 infection leads to herpes genitalis. While no effective vaccine is available, acyclovir is widely used for therapy, which targets and inhibits viral DNA polymerase. Although acyclovir is of low toxicity, resistant strains arise due to persistent use, mainly in immune compromised patients. In our effort to identify new HSV inhibitory molecules, harmine was found to potently inhibit HSV infection. Harmine, a beta-carbon alkaloid with an indole core structure and a pyridine ring, is widely distributed in plants. Earlier studies showed that harmine exhibited pharmacological activities such as antifungal, antimicrobial, antitumor, antiplasmodial and antioxidants. In the current study, we showed that harmine was a potent inhibitor of HSV-2 infection in vitro assays with EC50 value at around 1.47μM and CC50 value at around 337.10μM. The HSV RNA transcription, protein synthesis, and virus titers were reduced by the presence of harmine in a dose dependent manner. Further study on the mechanism of the anti-HSV activity showed that harmine blocked HSV-induced ROS production and the upregulated cytokine/chemokine expression, but our evidence showed that the inhibition of viral replication was unlikely mediated by the blocking of ROS production. We demonstrated that harmine significantly reduced HSV-2-induced NF-κB activation, as well as IκB-α degradation and p65 nuclear translocation. We found that harmine also inhibited HSV-2-mediated p38 kinase and c-Jun N-terminal kinases (JNK) phosphorylation.

Keywords: Antiviral activity; Harmine; Herpes simplex virus (HSV); MAPK pathways; Nuclear factor kappaB (NF-κB); ROS.

Harmine also down regulates TB which is actually the cause of Type-1 diabetes. People infected with TB used to die of Type-1 diabetes as the beta cells were killed off by a TB infection. Various Mycobacterium can inadvertantly activate the T-Cell immune response which mistakenly attacks beta cells in the pancreas:
--------
Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors
of Mycobacterium tuberculosis Phosphoserine Phosphatase

by Elise Pierson 1,*,†ORCID,Marie Haufroid 1,*,†ORCID,Tannu Priya Gosain 2,Pankaj Chopra 2ORCID,Ramandeep Singh 2 andJohan Wouters 1,*ORCID
1
Laboratoire de Chimie Biologique Structurale (CBS), Namur Medicine and Drug Innovation Center (NAMEDIC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (UNamur), B-5000 Namur, Belgium
2
Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, Faridabad 121001, Haryana, India
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Molecules 2020, 25(2), 415; https://doi.org/10.3390/molecules25020415
Received: 17 December 2019 / Revised: 14 January 2020 / Accepted: 15 January 2020 / Published: 19 January 2020

(This article belongs to the Special Issue Recent Advances in Antitubercular Drug Discovery)
Download Browse Figures Versions Notes
Abstract
Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants (Ki) values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2.

Keywords: M. tuberculosis; phosphoserine phosphatase; SerB2; 2,7,9-trisubstituted harmine derivatives
https://www.mdpi.com/1420-3049/25/2/415

A recent article on Harmine:
---------
Life (Basel). 2022 Dec 3;12(12):2022. doi: 10.3390/life12122022.

Harmine Inhibits Multiple TLR-Induced Inflammatory Expression through Modulation of NF-κB p65, JNK, and STAT1

So-Jung Jin 1, Youngju Song 2, Hong Shik Park 3, Kye Won Park 4, SeungGwan Lee 5, Hee Kang 5
Affiliations expand
PMID: 36556387 PMCID: PMC9787735 DOI: 10.3390/life12122022
Free PMC article

Abstract
Harmine is a beta-carboline alkaloid present in various plants, including in the seeds of Peganum harmala L. This study aimed to investigate the anti-inflammatory activity and mechanism of harmine using macrophages stimulated with various toll-like receptor (TLR) agonists and a model of endotoxemia. The expression of inflammatory mediators induced by ligands of TLRs 2, 3, 4, and 9 were examined in thioglycollate-elicited peritoneal macrophages isolated from BALB/c and C57BL/6 mouse strains. Further, the activation of NF-κB, MAPK, AP-1, and STAT1 was explored using lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly(I:C)). Finally, the liver inflammatory response during endotoxemia was examined. Harmine inhibited inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, and other markers induced by various TLR agonists. The inhibition of NF-κB activity by harmine occurred via the modulation of p65 phosphorylation, independent of IκBα degradation. The inhibition of AP-1 activity by harmine was associated with the modulation of JNK. Harmine inhibited the LPS-induced serine and tyrosine phosphorylation of STAT1, but only affected serine phosphorylation by poly(I:C) treatment. In vivo, harmine inhibited iNOS and COX-2 expression during endotoxemia. Collectively, the results show that harmine can be effective against infectious inflammation through modulation of NF-κB, JNK, and STAT1.

Keywords: AP-1; JNK; NF-κB; STAT1; TLR; TNF-α; harmine; iNOS; inflammation; macrophages.

https://pubmed.ncbi.nlm.nih.gov/36556387/

Proteomic changes induced by harmine in human brain organoids reveal signaling pathways related to neuroprotection

View ORCID ProfileKarina Karmirian, Lívia Goto-Silva, Juliana Minardi Nascimento, Marcelo N. Costa, José Alexandre Salerno, Isis Moraes Ornelas, Bart Vanderborght, Daniel Martins-de-Souza, Stevens Rehen

doi: https://doi.org/10.1101/2021.06.16.448740

This article is a preprint and has not been certified by peer review [what does this mean?].
0000009
AbstractFull TextInfo/HistoryMetrics Preview PDF

Abstract
Harmine is a β-carboline found in Banisteriopsis caapi, a constituent of ayahuasca brew. Ayahuasca is consumed as a beverage in native Americans’ sacred rituals and in religious ceremonies in Brazil. Throughout the years, the beneficial effects of ayahuasca to improve mental health and life quality have been reported, which propelled the investigation of its therapeutic potential to target neurological disorders such as depression and anxiety. Indeed, antidepressant effects of ayahuasca have been described, raising the question of which cellular mechanisms might underlie those effects. Previous animal studies describe potential neuroprotective mechanisms of harmine, including anti-inflammatory and antioxidant activities, and neurotrophin signaling activation. However, the cellular and molecular mechanisms modulated by harmine in human models remain less investigated. Here we analyzed the short-term changes in the proteome of human brain organoids treated with harmine using shotgun mass spectrometry. Harmine upregulates proteins related to synaptic vesicle cycle, cytoskeleton-dependent intracellular transport, cell cycle, glucose transporter-4 translocation, and neurotrophin signaling pathway. In addition, protein expression levels of Akt and phosphorylated CREB were increased after 24 hour-treatment. Our results shed light on the potential mechanisms that may underlie harmine-induced neuroprotective effects.

Introduction
Harmine is a β-carboline, first isolated in the 1840s from Peganum harmala (Syrian rue) seeds, which are used as medicinal plants in Eastern countries1,2. In America, harmine is found in Banisteriopsis caapi (cipó-mariri) and is consumed in ayahuasca, a traditional psychotropic brew originated in the Amazon Forest by indigenous people. Since 1930, it has been used in religious ceremonies of ‘Santo Daime’ and ‘União do Vegetal’ churches, and later on, it became popular among people searching for its anecdotal beneficial effects in mental health3,4. Indeed, antidepressant effects induced by ayahuasca have been described in a randomized placebo-controlled trial targeting treatmentresistant depression5.

Ayahuasca is prepared by the decoction of Banisteriopsis caapi vines and Psychotria viridis leaves6, resulting in a beverage containing β-carbolines (harmine, harmaline, and tetrahydroharmine) and the psychedelic compound N,N-dimethyltryptamine (N,N-DMT) derived from P. viridis. The concentration of these components varies widely within preparations7. Therefore, it is of utmost relevance to investigate the mechanisms triggered by each compound, separately, in order to understand the mechanisms promoting beneficial neurological effects.

Harmine crosses the blood-brain barrier and binds to serotonin receptors, mainly to 5HT2A, followed by 5HT2C8,9 In addition, harmine inhibits monoamine oxidase A/B (MAO-A/B) and dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)10,11. Since MAO-A/B catalyzes monoamine degradation, MAO inhibition elevates monoamine concentration in the synaptic cleft, which is one of the main mechanisms of action of antidepressant drugs12. DYRK1A is a major kinase associated with several functions during neurodevelopment, adult brain physiology, and neurodegenerative diseases13-15. Interestingly, DYRK1A inhibition has been described as a potential target for tauopathies and associated neurodegenerative diseases16.

Considering its molecular targets, harmine became a potential drug candidate for targeting neurological disorders or displaying neuroprotective effects. Indeed, several behavioral studies describe improvements in cognitive function mediated by acute or chronic treatment with harmine in mice models17-21. On a cellular level, harmine was found to stimulate the proliferation of neural progenitor cells, suggesting an effect in neurogenesis22. Further neuroprotective effects were also described in traumatic brain-injured mice, in which harmine treatment reduced the brain edema along with decreased levels of cell death and inflammatory markers in the hippocampus, leading to increased neuronal survival 23. Moreover, harmine displayed antioxidant effects, reducing lipid and protein oxidation along with increasing catalase and superoxide dismutase (SOD) activities in the prefrontal cortex and hippocampus of adult mice24. Besides the anti-inflammatory and antioxidant effects, harmine also modulates the neurotrophin signaling pathway by increasing brain-derived neurotrophic factor (BDNF) and phosphorylated TrkB protein levels in mice models20,21,25. Nonetheless, the effects of harmine in human neural cells remain less explored and investigating harmine effects in human models can bring new insights into harmine applications to treat neurological disorders.

Human brain organoids derived from induced pluripotent stem cells (iPSCs) exhibit structural and gene expression similarities with the human brain, recapitulating features of its cell diversity and cytoarchitecture26-28. Brain organoids have been used on neurological disease modeling, neurodevelopmental research, and drug screening29-32. Considering the wide range of applications, this model offers a great potential for translational research33. Here we analyzed proteomic alterations induced by short-term treatment with harmine in human brain organoids. We show that harmine alters proteins associated with heterocyclic compound binding, DNA replication, and antioxidant properties, which was expected considering the chemical structure of harmine and previous evidence supporting cell cycle regulation and antioxidant activity. Furthermore, we found that harmine modulates a wide range of processes including the synaptic vesicle cycle, protein folding, cytoskeletondependent transport, and glucose transporter-4 (GLUT4) translocation pathway. Harmine also upregulates AKT and increases p-CREB levels, indicating a positive regulation of the neurotrophin signaling pathway. Therefore, our findings help to confirm previously proposed mechanisms and describe novel pathways that may explain other potential effects triggered by harmine.

Results

Human brain organoids express harmine targets

First, we analyzed the basal expression of known harmine targets in human brain organoids at 45 days of formation (day-45). DYRK1A and 5HT2A mRNA expression was confirmed with qualitative PCR for the presence of specific bands at 80 and 359 bp, respectively (Fig. 1A). Then, DYRK1A and 5HT2A protein expression were evaluated by immunocytochemistry (ICC) (Fig. 1B, C). The pattern of DYRK1A staining was spread throughout the nuclei of brain organoid cells with notable labeling in proliferative zones, which was expected considering DYRK1A role in brain development (Fig. 1B). The proliferative zones are rosette-like structures enriched with neural progenitor cells distributed radially and positive for nestin (Fig. 2A). We also found 5HT2A positive cells spread over the brain organoid. Some microtubule-associated protein 2 (MAP2) positive cells exhibit 5HT2A staining, although 5HT2A was also expressed in MAP2 negative cells, indicating that its expression is not restricted to neurons (Fig. 1C).

https://www.biorxiv.org/content/10.1101/2021.06.16.448740v1.full

Another paper on how Harmine inhibits Herpes Simplex 2...if you use it...use it with a good Kefir...it double helps. I used to have massive hypoglycemia at 40 mg/dl test sugars...I can hit that now and see "bright lights" with normal conversation with anyone... Before it was sweats and flight or fight behaviors. Today I don't see that. The Brain's thinking, even with intense hypoglycemia, can be persevered with proper thinking with Harmine, and with Harmine you just see bright lights...and it tips you off directly that you have something to pay attention to (low blood sugar) and you are then in situations with an "aware" brain instead of sweats and panic with the dissolution of your immediate "reality" -- hypo-glycemia produces your "true" self. You can't misrepresent anything.  You can now see things more distant but immediate--Harmine cuts that tremendously...Essentially, the bright lights says.."I better check my blood-sugar or get some "juice" if things are too low. It helps indicate it in the brain. Basically it cures Type-3 diabetes--the Brain insulin panic (the brain is first served in all human body energy creation)--Harmine stops the panic. Your brain is kept safe and sound and mostly reasonable. Also, it greatly assists the "Brain" to receive energy first from ATP-Stomach bacteria-Type 3 Brain Insulin (80% of Stomach nerves are connect directly to the brain as energy is created in the gut (ATP) via bacteria )... Harmine helps cut the "panic" in the brain when hypoglycemia ensues...essentially it can reprogram the brain's reaction to not only infections but ATP creation...essentially the "brain" is served first so that Alzheimer's/Other infectious diseases are reduced in their impact first on the brain's functions. Basically the brain is kept supplied so it doesn't overreact with cascading hormone-glucagon releases. Harmine is beautiful and effective if used properly.  I've cured my hypo-glycemia to a great extent with it, even down to 20 mg/dl of sugars -- I still carried on coherent conversations--where as this is usually ambulance time for hypo-glycemics-T1-diabetics. It also can help beat cancer with the same DNA-RNA reprogramming...it essentially conserves ATP-Energy creation in the brain and body...and it can enhance Dopamine in the fore-brain which helps with focus and the mind's bearing on reality. It is better than MSM propaganda. If everyone around the world experienced intense hypo-glycemia (where reality as you know it is "lost")...there would be full peace on Earth... just a wink on that thought... It is a big un-orthodox Bio-Hack but it does work for me at least...and you can see things occasionally with great insight...it is likely is a great reset for Covid vaccines if taken since it protects the heart-brain:
-------------
Anti HSV-2 activity of Peganum harmala (L.) and isolation of the active compound
Author links open overlay panelRoudaina Benzekri a, Lamjed Bouslama a, Adele Papetti b, Majdi Hammami a, Abderrazak Smaoui c, Ferid Limam a

https://doi.org/10.1016/j.micpath.2017.12.017

Abstract

Genital herpes is a sexually transmitted disease caused by herpes simplex virus type 2 (HSV-2). Nucleoside analogues such as acyclovir (ACV) are the usual therapy for treating HSV infection. However, the overuse of this drug has led to the emergence of resistant strains. Therefore, the search for new alternative or complementary molecules to overcome this obstacle is needed. In this objective, Peganum harmala was investigated for its HSV-2 activity. The organic extracts of the different plant organs were evaluated for their cytotoxicity on Vero cells by the MTT test and anti HSV-2 activity by plaque reduction assay. Only the methanol seeds extract was active with a 50% inhibitory concentration (IC50) and a selectivity index (SI) of 161 and 13.2 μg/mL, respectively. In addition, the study of the antiviral mode of action revealed that this extract exerts a virucidal action both during the entry of viruses and the release of the newly formed virions, whereas no cell protection effect was observed. The active compound was isolated by bio-guided purification using thin layer chromatography (TLC) and identified by GC-MS and HPLC-DAD-ESI-MSn as harmine. The combination of harmine standard compound with ACV showed a combination index (CI) of 0.5 indicating that these two compounds have a synergic effect. This data suggests that harmine could be associated to ACV to improve the treatment of genital herpes essentially for the immunocompromised patients.

Graphical abstract
Image 1
Download : Download high-res image (213KB)
Download : Download full-size image

Introduction
Genital herpes is a sexually transmitted disease, generally caused by herpes simplex virus type 2 (HSV-2) that remains a worldwide problem. HSV-2 infects the genital mucosa and causes a painful ulcers and lesions around the genital tract [1]. After the primary infection, HSV-2 establishes a life-long latency infection within sensory dorsal root ganglia [2]. In addition, HSV-2 infection is associated to three fold increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition [3]. The common therapy for treatment of HSV infection is based on nucleoside analogues such as acyclovir (ACV) which is a guanosine analogue that inhibits the viral DNA polymerase. This molecule requires activation through triphosphorylation. The first phosphorylation is mediated by viral thymidine kinase whereas subsequent phosphorylations are achieved by host cellular thymidine kinases. However, the overuse of these anti-herpes drugs has led to the emergence of new mutants by the apparition of mutations in the UL23 gene coding for the thymidine kinase. The resistance has been mainly reported among immunocompromised patients [4]. Therefore, to remediate these drawbacks, the discovery of new molecules from medicinal plants as alternative to the available antivirals is needed.

Peganum harmala (L.) known as Harmal, Wild rue or Syrian rue, is a medicinal plant initially belonging to the Zygophyllaceae family [5], but was recently included in the Nitrariaceae family [6]. Peganum harmala is widely distributed in North Africa, Middle East and Australia [7]. The aerial parts and the seeds of this plant have been used in folk medicine as an abortifacient, emmenagogue, anti-inflammatory and analgesic agent [8], and also for the treatment of asthma, rheumatoid arthritis [9]. Several pharmacological studies focused on Peganum harmala seeds showed that alkaloids belonging to the β-carboline family such as harmine, harmaline, harman, harmol, and harmalol could be considered as responsible for a wide range of pharmacological effects as gastro and hepato-protective [10], [11], antispasmodic, anticholinergic [12], [13], cardiovascular and vasorelaxant [14] effects. Other studies reported that Peganum harmala exhibited antibacterial, antifungal [15] as well as anti-leishmania [16] and antitumor activities [17], [18]. Furthermore, hypothermic and hallucinogenic properties have been also ascribed to this plant [19].

In this study, different organic extracts of each Peganum harmala organ (seed, stem, leaf, and flower) were investigated for the evaluation of anti HSV-2 activity. The mode of action of the active extract was also studied and the compound responsible for the tested activity was isolated by bio-guided assays and identified by chromatographic methods coupled with mass spectrometry.

Section snippets
Chemicals and reagents
Hexane, dichloromethane, ethyl acetate, methanol, ethanol and dimethyl sulfoxide (DMSO) were purchased from Lab Scan, Poland. Media for cell culture, i.e. RPMI 1640, fetal bovine serum (FBS), l-glutamine (200 mM), antibiotics-antimicotic (100 X), phosphate-buffered saline (PBS) and Trypsine-EDTA (10 X) were purchased from Gibco, USA; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) from Bio Basic, Canada; harmine, acyclovir, methyl cellulose and crystal violet from

Cytotoxicity and anti-HSV-2 activity of Peganum harmala extracts
The cytotoxicity of the 16 extracts obtained from Peganum harmala was evaluated by the determination of their CC50 (Table 1). Globally, the methanol extracts showed less cytotoxicity. Furthermore, methanol seeds extract was the only one that exhibited an anti HSV-2 activity with 100% of viral inhibition at CC50/2 value. Fig. 1 showed the evolution of the percentage of viral inhibition depending on the concentration of this active extract (from CC50/2). The IC50 obtained by linear regression

Discussion
Herpes Simplex Virus-2 (HSV-2) causes genital disease that may be chronic and persistent. Acyclovir is an antiviral drug used for the treatment of this infection. However, this medicine is not active both against strains which developed a form of resistance and viruses at latency stage which genome has been incorporated into a host chromosomal DNA during a primary infection. Therefore, the search for new alternative or complementary antivirals is required and plants constitute a reservoir of

Conclusion
Peganum harmala (L.) was investigated for its HSV-2 activity. From the sixteen organic extracts from the different organs, only the methanol seed extract exhibited activity. This active extract showed a virucidal action both during the entry of viruses and the release of the newly formed virions. Tests carried out on other viruses confirmed that this extract seems to act on enveloped viruses probably by blocking specific receptors involved in the recognition and the binding of their target cell.

https://www.sciencedirect.com/science/article/abs/pii/S0882401017310860

Background on the Vagus Nerve and appendages -- it is the core of your "sense of self" and sense of the world at large:
----------
Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

imageSigrid Breit1† imageAleksandra Kupferberg1† imageGerhard Rogler2 imageGregor Hasler1*

1Division of Molecular Psychiatry, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland
2Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.

Introduction

The bidirectional communication between the brain and the gastrointestinal tract, the so-called “brain–gut axis,” is based on a complex system, including the vagus nerve, but also sympathetic (e.g., via the prevertebral ganglia), endocrine, immune, and humoral links as well as the influence of gut microbiota in order to regulate gastrointestinal homeostasis and to connect emotional and cognitive areas of the brain with gut functions (1). The ENS produces more than 30 neurotransmitters and has more neurons than the spine. Hormones and peptides that the ENS releases into the blood circulation cross the blood–brain barrier (e.g., ghrelin) and can act synergistically with the vagus nerve, for example to regulate food intake and appetite (2). The brain–gut axis is becoming increasingly important as a therapeutic target for gastrointestinal and psychiatric disorders, such as inflammatory bowel disease (IBD) (3), depression (4), and posttraumatic stress disorder (PTSD) (5). The gut is an important control center of the immune system and the vagus nerve has immunomodulatory properties (6). As a result, this nerve plays important roles in the relationship between the gut, the brain, and inflammation. There are new treatment options for modulating the brain–gut axis, for example, vagus nerve stimulation (VNS) and meditation techniques. These treatments have been shown to be beneficial in mood and anxiety disorders (7–9), but also in other conditions associated with increased inflammation (10). In particular, gut-directed hypnotherapy was shown to be effective in both, irritable bowel syndrome and IBD (11, 12). Finally, the vagus nerve also represents an important link between nutrition and psychiatric, neurological and inflammatory diseases.

Basic Anatomy of the Vagus Nerve

The vagus nerve carries an extensive range of signals from digestive system and organs to the brain and vice versa. It is the tenth cranial nerve, extending from its origin in the brainstem through the neck and the thorax down to the abdomen. Because of its long path through the human body, it has also been described as the “wanderer nerve” (13).

The vagus nerve exits from the medulla oblongata in the groove between the olive and the inferior cerebellar peduncle, leaving the skull through the middle compartment of the jugular foramen. In the neck, the vagus nerve provides required innervation to most of the muscles of the pharynx and larynx, which are responsible for swallowing and vocalization. In the thorax, it provides the main parasympathetic supply to the heart and stimulates a reduction in the heart rate. In the intestines, the vagus nerve regulates the contraction of smooth muscles and glandular secretion. Preganglionic neurons of vagal efferent fibers emerge from the dorsal motor nucleus of the vagus nerve located in the medulla, and innervate the muscular and mucosal layers of the gut both in the lamina propria and in the muscularis externa (14). The celiac branch supplies the intestine from proximal duodenum to the distal part of the descending colon (15, 16). The abdominal vagal afferents, include mucosal mechanoreceptors, chemoreceptors, and tension receptors in the esophagus, stomach, and proximal small intestine, and sensory endings in the liver and pancreas. The sensory afferent cell bodies are located in nodose ganglia and send information to the nucleus tractus solitarii (NTS) (see Figure 1). The NTS projects, the vagal sensory information to several regions of the CNS, such as the locus coeruleus (LC), the rostral ventrolateral medulla, the amygdala, and the thalamus (14).

Figure 1
www.frontiersin.org

FIGURE 1. Overview over the basic anatomy and functions of the vagus nerve.

The vagus nerve is responsible for the regulation of internal organ functions, such as digestion, heart rate, and respiratory rate, as well as vasomotor activity, and certain reflex actions, such as coughing, sneezing, swallowing, and vomiting (17). Its activation leads to the release of acetylcholine (ACh) at the synaptic junction with secreting cells, intrinsic nervous fibers, and smooth muscles (18). ACh binds to nicotinic and muscarinic receptors and stimulates muscle contractions in the parasympathetic nervous system.

Animal studies have demonstrated a remarkable regeneration capacity of the vagus nerve. For example, subdiaphragmatic vagotomy induced transient withdrawal and restoration of central vagal afferents as well as synaptic plasticity in the NTS (19). Further, the regeneration of vagal afferents in rats can be reached 18 weeks after subdiaphragmatic vagotomy (20), even though the efferent reinnervation of the gastrointestinal tract is not restored even after 45 weeks (21).

Functions of the Vagus Nerve

The Role of Vagus in the Functions of the Autonomic Nervous System
Alongside the sympathetic nervous system and the enteric nervous system (ENS), the parasympathetic nervous system represents one of the three branches of the autonomic nervous system.

The definition of the sympathetic and parasympathetic nervous systems is primarily anatomical. The vagus nerve is the main contributor of the parasympathetic nervous system. Other three parasympathetic cranial nerves are the nervus oculomotorius, the nervus facialis, and the nervus glossopharyngeus.

The most important function of the vagus nerve is afferent, bringing information of the inner organs, such as gut, liver, heart, and lungs to the brain. This suggests that the inner organs are major sources of sensory information to the brain. The gut as the largest surface toward the outer world and might, therefore, be a particularly important sensory organ.

Historically, the vagus has been studied as an efferent nerve and as an antagonist of the sympathetic nervous system. Most organs receive parasympathetic efferents through the vagus nerve and sympathetic efferents through the splanchnic nerves. Together with the sympathetic nervous systems, the parasympathetic nervous system is responsible for the regulation of vegetative functions by acting in opposition to each other (22). The parasympathetic innervation causes a dilatation of blood vessels and bronchioles and a stimulation of salivary glands. On the contrary, the sympathetic innervation leads to a constriction of blood vessels, a dilatation of bronchioles, an increase in heart rate, and a constriction of intestinal and urinary sphincters. In the gastrointestinal tract, the activation of the parasympathetic nervous system increases bowel motility and glandular secretion. In contrast to it, the sympathetic activity leads to a reduction of intestinal activity and a reduction of blood flow to the gut, allowing a higher blood flow to the heart and the muscles, when the individual faces existential stress.

The ENS arises from neural crest cells of the primarily vagal origin and consists of a nerve plexus embedded in the intestinal wall, extending across the whole gastrointestinal tract from the esophagus to the anus. It is estimated that the human ENS contains about 100–500 million neurons. This is the largest accumulation of nerve cells in the human body (23–25). Since the ENS is similar to the brain regarding structure, function, and chemical coding, it has been described as “the second brain” or “the brain within the gut” (26). It consists of two ganglionated plexuses—the submucosal plexus, which regulates gastrointestinal blood flow and controls the epithelial cell functions and secretion and the myenteric plexus, which mainly regulates the relaxation and contraction of the intestinal wall (23). The ENS serves as intestinal barrier and regulates the major enteric processes, such as immune response, detecting nutrients, motility, microvascular circulation, and epithelial secretion of fluids, ions, and bioactive peptides (27). There clearly is “communication” between the vagal nerve and the ENS, and the main transmitter is cholinergic activation through nicotinic receptors (24). Interaction of ENS and the vagal nerve as a part of the CNS leads to a bidirectional flow of information. On the other hand, the ENS in the small and large bowel also is able to function quite independent of vagal control as it contains full reflex circuits, including sensory neurons and motor neurons. They regulate muscle activity and motility, fluid fluxes, mucosal blood flow, and also mucosal barrier function. ENS neurons are also in close contact to cells of the adaptive and innate immune system and regulate their functions and activities. Aging and cell loss in the ENS are associated with complaints, such as constipation, incontinence, and evacuation disorders. The loss of the ENS in the small and large intestine may be life threatening (Hirschsprung’s disease; intestinal pseudo-obstruction), whereas as loss of the vagal nerve in these areas is not.

Vagus Nerve as a Link between the Central and ENS

The connection between the CNS and the ENS, also referred to as the brain–gut axis enables the bidirectional connection between the brain and the gastrointestinal tract. It is responsible for monitoring the physiological homeostasis and connecting the emotional and cognitive areas of the brain with peripheral intestinal functions, such as immune activation, intestinal permeability, enteric reflex, and enteroendocrine signaling (1). This brain–gut axis, includes the brain, the spinal cord, the autonomic nervous system (sympathetic, parasympathetic, and ENS), and the hypothalamic–pituitary–adrenal (HPA) axis (1). The vagal efferents send the signals “down” from brain to gut through efferent fibers, which account for 10–20% of all fibers and the vagal afferents “up” from the intestinal wall to the brain accounting for 80–90% of all fibers (28) (see Figure 1). The vagal afferent pathways are involved in the activation/regulation of the HPA axis (29), which coordinates the adaptive responses of the organism to stressors of any kind (30). Environmental stress, as well as elevated systemic proinflammatory cytokines, activates the HPA axis through secretion of the corticotropin-releasing factor (CRF) from the hypothalamus (31). The CRF release stimulates adrenocorticotropic hormone (ACTH) secretion from pituitary gland. This stimulation, in turn, leads to cortisol release from the adrenal glands. Cortisol is a major stress hormone that affects many human organs, including the brain, bones, muscles, and body fat.

Both neural (vagus) and hormonal (HPA axis) lines of communication combine to allow brain to influence the activities of intestinal functional effector cells, such as immune cells, epithelial cells, enteric neurons, smooth muscle cells, interstitial cells of Cajal, and enterochromaffin cells (32). These cells, on the other hand, are under the influence of the gut microbiota. The gut microbiota has an important impact on the brain–gut axis interacting not only locally with intestinal cells and ENS, but also by directly influencing neuroendocrine and metabolic systems (33). Emerging data support the role of microbiota in influencing anxiety and depressive-like behaviors (34). Studies conducted on germ-free animals demonstrated that microbiota influence stress reactivity and anxiety-like behavior and regulate the set point for HPA activity. Thus, these animals generally show a decreased anxiety (35) and an increased stress response with augmented levels of ACTH and cortisol (36).

In case of food intake, vagal afferents innervating the gastrointestinal tract provide a rapid and discrete account of digestible food as well as circulating and stored fuels, while vagal efferents together with the hormonal mechanisms codetermine the rate of nutrient absorption, storage, and mobilization (37). Histological and electrophysiological evidence indicates that visceral afferent endings of the vagus nerve in the intestine express a diverse array of chemical and mechanosensitive receptors. These receptors are targets of gut hormones and regulatory peptides that are released from enteroendocrine cells of the gastrointestinal system in response to nutrients, by distension of the stomach and by neuronal signals (38). They influence the control of food intake and regulation of satiety, gastric emptying and energy balance (39) by transmitting signals arising from the upper gut to the nucleus of the solitary tract in the brain (40). Most of these hormones, such as peptide cholecystokinin (CCK), ghrelin, and leptin are sensitive to the nutrient content in the gut and are involved in regulating short-term feelings of hunger and satiety (41).

More at link: https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00044/full
https://www.livescience.com/vagus-nerve.html#section-vagus-nerve-stimulation-as-medical-treatment

Stimulating the vagus nerve: memories are made of this

Psychobiologists show how the vagal pathway links hormones outside the brain to neurotransmitters inside the brain to lock in memory of emotional or stressful events.

By RACHEL ADELSON

April 2004, Vol 35, No. 4

Print version: page 36

5 min read

0
University of Virginia psychologists have moved the science of memory forward, reporting that stimulating the vagus nerve, which carries sensory messages to and from the brain, releases the neurotransmitter norepinephrine into the amygdala, strengthening memory storage in limbic regions of the brain that regulate arousal, memory and feeling responses to emotionally laden stimuli.

Their findings, which appear in the February issue of Behavioral Neuroscience (Vol. 118, No. 1), outline the neural pathway through which hormones that are released in the body affect specific parts of the brain during meaningful or emotionally arousing events in order to strengthen memories that will later foster sentimental pleasure or torture us with relived trauma.

The researchers--psychobiologists Cedric L.Williams, PhD, Derrick Hassert, PhD, and Teiko Miyashita, PhD--conclude that the vagus nerve is the "missing link" between the hormone epinephrine outside the brain and the neurotransmitter norepinephrine inside the brain.

"It had always been puzzling how the peripheral release of epinephrine could have these central effects on memory," says John Disterhoft, PhD, editor of Behavioral Neuroscience and a neurobiologist at Northwestern University. "This work helps us to understand how arousal responses in the body periphery, such as fight or flight, affect the brain--which they must if they are going to enhance learning as much as they are known to do."

Armed with these new insights, scientists can now more carefully calibrate how they stimulate the vagus nerve to influence the release of norepinephrine, flood the amygdala and strengthen memory. Or they can pursue more efficient blockers to shut out intrusive memories. The implications are many, offering explanations of known phenomena and holding out hope for improved treatments.

Juicing up the brain

Given mounting evidence of vagal nerve interaction with brain biochemistry, the University of Virginia researchers sought direct experimental evidence that stimulating the nerve can cause specific changes in neurotransmitter release.

In the first of two experiments using 31 rats total, the researchers surgically implanted electrodes around the left-side vagus nerve. During surgery, they also implanted a microdialysis device that allowed them to sample the concentration of norepinephrine that is released in the amygdala during rest or following vagal stimulation.

Williams and his colleagues stimulated the vagus nerve at a level previously reported by Robert A. Jensen, PhD, his graduate adviser, to improve memory in both laboratory rats (0.4 microAmps for 30 seconds) and humans (0.5 microAmps for 30 seconds). For more than two hours, they collected brain-fluid samples every 20 minutes. In the first experiment, norepinephrine levels increased by 71 percent in the first 20 minutes after the voltage jump and peaked after 140 minutes at a 128-percent increase above baseline. Nothing changed in the unstimulated control group.

This experiment supported the researchers' first hypothesis, that vagal nerve stimulation produces dramatic surges in norepinephrine in a brain area involved with memory storage, a finding that almost certainly generalizes to humans. What's more, Williams says, "The magnitude and time course of changes in amygdala norepinephrine almost mirrored the changes produced by the dose of epinephrine that has been shown to improve memory."

In the second experiment, the researchers injected the rats with methyl atropine, a drug that blocks the acetylcholine that is released from descending vagal fibers onto peripheral organs, 10 minutes before stimulating the vagus nerve. The blocker--which affects the descending (efferent) fibers of the vagus nerve--didn't change the release of norepinephrine any more than did a control solution of saline.

The authors conclude that the findings rule out any role played by negative feedback from the periphery and confirm that the vagus nerve--albeit the ascending fibers--is the mechanism by which peripheral epinephrine activates the release of brain norepinephrine during memory consolidation.

The research solves the mystery of how the adrenal gland could stimulate the release of norepinephrine in the brain, observers say. During stress, the adrenal medulla (near the kidneys) in humans and rats releases epinephrine into the bloodstream, famously causing the "fight-or-flight" response in the heart, lungs, stomach and elsewhere. However, epinephrine can't cross the blood-brain barrier. So what is the switch that turns on epinephrine? The vagus nerve.

The new evidence provides a close-up look at how emotional events affect the body to influence how well the brain encodes information about exciting or meaningful events. First, emotionally arousing events stimulate the nervous system to release epinephrine. Unable to get into the brain, it does the next best thing: It activates the ascending fibers of the vagus nerve, which in turn stimulate brain neurons in an area of the brainstem known as the nucleus of the solitary tract (NTS).

In this model, NTS neurons release norepinephrine into brain structures that process memory, such as the amygdala and hippocampus. Upon activation, these memory-related regions work harder to properly put the attributes of emotionally arousing experiences into long-term storage.

From vagus to specific

At their most basic, the findings help explain a prior decade of data on how stimulating the vagus nerve (either of the 10th pair of cranial nerves) improves memory processing of recently acquired information.

"These findings fit well with extensive previous evidence that epinephrine regulates memory consolidation, acting via the vagus nerve; that neurons from the NTS release norepinephrine in the amygdala; and that norepinephrine release in the amygdala plays a critical role in regulating the strength of memories," says James McGaugh, PhD, director of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine, and author of the recent "Memory and Emotion: The Making of Lasting Memories" (Columbia University Press, 2003).

More at link: https://www.apa.org/monitor/apr04/vagus

Apparently there are devices for Vagus nerve stimulation. Never bought or tried a device but they exist for a couple hundred dollars. Example: https://pulsetto.tech/
------
Published: January 1999

Enhanced recognition memory following vagus nerve stimulation in human subjects

Kevin B. Clark, Dean K. Naritoku, Douglas C. Smith, Ronald A. Browning & Robert A. Jensen
Nature Neuroscience volume 2, pages94–98 (1999)Cite this article

3383 Accesses

393 Citations

33 Altmetric

Metricsdetails

Abstract
Neuromodulators associated with arousal modulate learning and memory, but most of these substances do not freely enter the brain from the periphery. In rodents, these neuromodulators act in part by initiating neural messages that travel via the vagus nerve to the brain, and electrical stimulation of the vagus enhances memory. We now extend that finding to human verbal learning. We examined word-recognition memory in patients enrolled in a clinical study evaluating the capacity of vagus nerve stimulation to control epilepsy. Stimulation administered after learning significantly enhanced retention. These findings confirm in humans the hypothesis that vagus nerve activation modulates memory formation similarly to arousal.

https://www.nature.com/articles/nn0199_94

Channelrhodopsin


From Wikipedia, the free encyclopedia

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels.[1] They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light.[2] Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes (see optogenetics). Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions (ACRs, KCRs) have been cloned from other species of algae and protists.

History

Phototaxis and photoorientation of microalgae have been studied over more than a hundred years in many laboratories worldwide. In 1980, Ken Foster developed the first consistent theory about the functionality of algal eyes.[3] He also analyzed published action spectra and complemented blind cells with retinal and retinal analogues, which led to the conclusion that the photoreceptor for motility responses in Chlorophyceae is rhodopsin.[4]
....


Development as a molecular tool

In 2005, three groups sequentially established ChR2 as a tool for genetically targeted optical remote control (optogenetics) of neurons, neural circuits and behavior.

At first, Karl Deisseroth's lab demonstrated that ChR2 could be deployed to control mammalian neurons in vitro, achieving temporal precision on the order of milliseconds (both in terms of delay to spiking and in terms of temporal jitter).[19] Because all opsins require retinal as the light-sensing co-factor and it was unclear whether central mammalian nerve cells would contain sufficient retinal levels, but they do. It also showed, despite the small single-channel conductance, sufficient potency to drive mammalian neurons above action potential threshold. From this, channelrhodopsin became the first optogenetic tool, with which neural activity could be controlled with the temporal precision at which neurons operate (milliseconds). A second study was published later confirming the ability of ChR2 to control the activity of vertebrate neurons, at this time in the chick spinal cord.[20] This study was the first wherein ChR2 was expressed alongside an optical silencer, vertebrate rhodopsin-4 in this case, demonstrating for the first time that excitable cells could be activated and silenced using these two tools simultaneously, illuminating the tissue at different wavelengths.

It was demonstrated that ChR2, if expressed in specific neurons or muscle cells, can evoke predictable behaviors, i.e. can control the nervous system of an intact animal, in this case the invertebrate C. elegans.[21] This was the first using ChR2 to steer the behavior of an animal in an optogenetic experiment, rendering a genetically specified cell type subject to optical remote control. Although both aspects had been illustrated earlier that year by the group of Gero Miesenböck, deploying the indirectly light-gated ion channel P2X2,[22] it was henceforth microbial opsins like channelrhodopsin that dominated the field of genetically targeted remote control of excitable cells, due to the power, speed, targetability, ease of use, and temporal precision of direct optical activation, not requiring any external chemical compound such as caged ligands.[23]

To overcome its principal downsides — the small single-channel conductance (especially in steady-state), the limitation to one optimal excitation wavelength (~470 nm, blue) as well as the relatively long recovery time, not permitting controlled firing of neurons above 20–40 Hz — ChR2 has been optimized using genetic engineering. A point mutation H134R (exchanging the amino acid Histidine in position 134 of the native protein for an Arginine) resulted in increased steady-state conductance, as described in a 2005 paper that also established ChR2 as an optogenetic tool in C. elegans.[21] In 2009, Roger Tsien's lab optimized ChR2 for further increases in steady-state conductance and dramatically reduced desensitization by creating chimeras of ChR1 and ChR2 and mutating specific amino acids, yielding ChEF and ChIEF, which allowed the driving of trains of action potentials up to 100 Hz.[24][25] In 2010, the groups of Hegemann and Deisseroth introduced an E123T mutation into native ChR2, yielding ChETA, which has faster on- and off-kinetics, permitting the control of individual action potentials at frequencies up to 200 Hz (in appropriate cell types).[26][24]

The groups of Hegemann and Deisseroth also discovered that the introduction of the point mutation C128S makes the resulting ChR2-derivative a step-function tool: Once "switched on" by blue light, ChR2(C128S) stays in the open state until it is switched off by yellow light – a modification that deteriorates temporal precision, but increases light sensitivity by two orders of magnitude.[27] They also discovered and characterized VChR1 in the multicellular algae Volvox carteri. VChR1 produces only tiny photocurrents, but with an absorption spectrum that is red-shifted relative to ChR2.[28] Using parts of the ChR1 sequence, photocurrent amplitude was later improved to allow excitation of two neuronal populations at two distinct wavelengths.[29]

Deisseroth's group has pioneered many applications in live animals such as genetically targeted remote control in rodents in vivo,[30] the optogenetic induction of learning in rodents,[31] the experimental treatment of Parkinson's disease in rats,[32][33] and the combination with fMRI (opto-fMRI).[34] Other labs have pioneered the combination of ChR2 stimulation with calcium imaging for all-optical experiments,[35] mapping of long-range[36] and local[37] neural circuits, ChR2 expression from a transgenic locus – directly[38] or in the Cre-lox conditional paradigm[37] – as well as the two-photon excitation of ChR2, permitting the activation of individual cells.[39][40][41]

In March 2013, the Brain Prize (Grete Lundbeck European Brain Research Prize) was jointly awarded to Bamberg, Boyden, Deisseroth, Hegemann, Miesenböck, and Nagel for "their invention and refinement of optogenetics".[42] The same year, Hegemann and Nagel received the Louis-Jeantet Prize for Medicine for "the discovery of channelrhodopsin". In 2015, Boyden and Deisseroth received the Breakthrough Prize in Life Sciences and in 2020, Miesenböck, Hegemann and Nagel received the Shaw prize in Life Science and Medicine for the development of optogenetics.

More at link: https://en.wikipedia.org/wiki/Channelrhodopsin

Synthetic telepathy

In a $6.3 million US Army initiative to invent devices for telepathic communication, Gerwin Schalk, underwritten in a $2.2 million grant, found the use of ECoG signals can discriminate the vowels and consonants embedded in spoken and imagined words, shedding light on the distinct mechanisms associated with production of vowels and consonants, and could provide the basis for brain-based communication using imagined speech.[101][154]

In 2002 Kevin Warwick had an array of 100 electrodes fired into his nervous system in order to link his nervous system into the Internet to investigate enhancement possibilities. With this in place Warwick successfully carried out a series of experiments. With electrodes also implanted into his wife's nervous system, they conducted the first direct electronic communication experiment between the nervous systems of two humans.[155][156][157][158]

Another group of researchers was able to achieve conscious brain-to-brain communication between two people separated by a distance using non-invasive technology that was in contact with the scalp of the participants. The words were encoded by binary streams using the sequences of 0's and 1's by the imaginary motor input of the person "emitting" the information. As the result of this experiment, pseudo-random bits of the information carried encoded words "hola" ("hi" in Spanish) and "ciao" ("goodbye" in Italian) and were transmitted mind-to-mind between humans separated by a distance, with blocked motor and sensory systems, which has low to no probability of this happening by chance.[159]

In the 1960s a researcher was successful after some training in using EEG to create Morse code using their brain alpha waves. Research funded by the US army is being conducted with the goal of allowing users to compose a message in their head, then transfer that message with just the power of thought to a particular individual.[160] On 27 February 2013 the group with Miguel Nicolelis at Duke University and IINN-ELS successfully connected the brains of two rats with electronic interfaces that allowed them to directly share information, in the first-ever direct brain-to-brain interface.[161][162][163]

https://en.wikipedia.org/wiki/Brain%E2%80%93computer_interface