# brain: the drug ISRIB reverses age-related cognitive decline within days (in mice) and even enhance cognition in healthy animals

<< Just a few doses of an experimental drug can reverse age-related declines in memory and mental flexibility in mice, (..)  The drug, called ISRIB (ISR InhiBitor), has already been shown in laboratory studies to restore memory function months after traumatic brain injury (TBI), reverse cognitive impairments in Down Syndrome , prevent noise-related hearing loss, fight certain types of prostate cancer , and even enhance cognition in healthy animals. >>

<< In the new study, researchers showed rapid restoration of youthful cognitive abilities in aged mice, accompanied by a rejuvenation of brain and immune cells that could help explain improvements in brain function. >>

<< ISRIB's extremely rapid effects show for the first time that a significant component of age-related cognitive losses may be caused by a kind of reversible physiological "blockage" rather than more permanent degradation, >> Susanna Rosi.

<< The data suggest that the aged brain has not permanently lost essential cognitive capacities, as was commonly assumed, but rather that these cognitive resources are still there but have been somehow blocked, trapped by a vicious cycle of cellular stress, (..)  Our work with ISRIB demonstrates a way to break that cycle and restore cognitive abilities that had become walled off over time. >> Peter Walter.

Drug reverses age-related cognitive decline within days. University of California, San Francisco. Dec 01, 2020.

https://medicalxpress.com/news/2020-12-drug-reverses-age-related-cognitive-decline.html

Karen Krukowski, Amber Nolan, et al. 

Small molecule cognitive enhancer reverses age-related memory decline in mice. eLife. doi: 10.7554/ eLife.62048. Dec 1, 2020.

https://elifesciences.org/articles/62048  

# brain: the hypothesis that a brain organoid (a lab-grown brain) can reach consciousness.

<< In Alysson Muotri’s laboratory, hundreds of miniature human brains, the size of sesame seeds, float in Petri dishes, sparking with electrical activity. 

These tiny structures, known as brain organoids, are grown from human stem cells and have become a familiar fixture in many labs that study the properties of the brain. Muotri, a neuroscientist at the University of California, San Diego (UCSD), has found some unusual ways to deploy his. He has connected organoids to walking robots, modified their genomes with Neanderthal genes, launched them into orbit aboard the International Space Station, and used them as models to develop more human-like artificial-intelligence (AI) systems. (..) But one experiment has drawn more scrutiny than the others. In August 2019, Muotri’s group published a paper in Cell Stem Cell (*) reporting the creation of human brain organoids that produced coordinated waves of activity, resembling those seen in premature babies. The waves continued for months before the team shut the experiment down. This type of brain-wide, coordinated electrical activity is one of the properties of a conscious brain. >> 

Sara Reardon. Can lab-grown brains become conscious? Nature 586, 658-661. doi: 10.1038/ d41586-020-02986-y. Oct 27, 2020. Correction Nov 4, 2020.

https://www.nature.com/articles/d41586-020-02986-y     

(*)  Trujillo CA, Gao R, et al. Complex Oscillatory Waves Emerging from Cortical Organoids Model Early Human Brain Network Development. Cell Stem Cell. 2019 Oct 3;25(4):558-569.e7. doi: 10.1016/ j.stem.2019.08.002. Aug 29, 2019. 

https://pubmed.ncbi.nlm.nih.gov/31474560/

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30337-6

# brain: flies, mice and humans, comparable behaviors for balance and motor control

<< Comparative developmental genetics indicate insect and mammalian forebrains form and function in comparable ways. However, these data are open to opposing interpretations that advocate either a single origin of the brain and its adaptive modification during animal evolution; or multiple, independent origins of the many different brains present in extant Bilateria. Here, (AA) describe conserved regulatory elements that mediate the spatiotemporal expression of developmental control genes directing the formation and function of midbrain circuits in flies, mice, and humans. These circuits develop from corresponding midbrain-hindbrain boundary regions and regulate comparable behaviors for balance and motor control. (They) findings suggest that conserved regulatory mechanisms specify cephalic circuits for sensory integration and coordinated behavior common to all animals that possess a brain. >>

Jessika C. Bridi, Zoe N. Ludlow, et al. Ancestral regulatory mechanisms specify conserved midbrain circuitry in arthropods and vertebrates. PNAS. doi: 10.1073/ pnas.1918797117. Aug 3, 2020.

https://www.pnas.org/content/early/2020/07/31/1918797117  

Humans and flies employ very similar mechanisms for brain development and function. King's College London.  Aug 3, 2020.

https://phys.org/news/2020-08-humans-flies-similar-mechanisms-brain.html

Also

'mosca in bottiglia' in: 2066 - voli a casaccio. Notes. Oct 01, 2006.   (quasi-stochastic poetry)

https://inkpi.blogspot.com/2006/10/2066-voli-casaccio.html

Also

keyword 'flies' in FonT

https://flashontrack.blogspot.com/search?q=flies

# behav: persistent neuronal firing during flight in flies, like a pulsating gambler who has to decide quickly

<< A general principle of sensory systems is that they adapt to prolonged stimulation by reducing their response over time. >>

<< as opposed to most sensory and visual neurons, and in particular to the motion vision sensitive neurons in the brains of both flies and mammals, the descending neurons show little adaption during stimulus motion. (..) the optic-flow-sensitive descending neurons display persistent firing, or an after-effect, following the cessation of visual stimulation, consistent with the lingering calcium signal hypothesis. >>

AA results << show a combination of adaptation and persistent firing in the neurons that project to the thoracic ganglia and thereby control behavioral output. >>

Sarah Nicholas, Karin Nordstrom. Persistent Firing and Adaptation in Optic-Flow-Sensitive Descending Neurons. Curr Biol. doi: 10.1016/ j.cub.2020.05.019. May 28, 2020.

https://www.cell.com/current-biology/fulltext/S0960-9822(20)30658-8

Revealing how flies make decisions on the fly to survive. Flinders University. May 28, 2020

https://phys.org/news/2020-05-revealing-flies-decisions-survive.html

Also

the flexible mental maps of flies. FonT. Nov 21, 2019. 

https://flashontrack.blogspot.com/2019/11/brain-flexible-mental-maps-of-flies.html

<< Considerando invece l' immagine classica della "mosca nella bottiglia", >>  in: 2066 - voli a casaccio. Notes. (quasi-stochastic poetry). Oct 01, 2006.

https://inkpi.blogspot.com/2006/10/2066-voli-casaccio.html

# pharma: drawing 'magic strings' for GPCRs

<< Psychedelics such as LSD and magic mushrooms have proven highly effective in treating depression and post-traumatic stress disorders, but medical use of these drugs is limited by the hallucinations they cause. >>

<< What if we could redesign drugs to keep their benefits while eliminating their unwanted side effects? >> Ron O.  Dror. 

<< Dror's team describes discoveries that could be used to minimize or eliminate side effects in a broad class of drugs that target G protein-coupled receptors, or GPCRs. GPCRs are proteins found in all human cells. LSD and other psychedelics are molecules that attach to GPCRs, as are about a third of all prescription drugs, including antihistamines, beta blockers and opioids. So important is this molecular mechanism that Stanford professor Brian Kobilka shared the 2012 Nobel Prize in Chemistry for his role in discovering how GPCRs work. >>

Tom Abate. What if we could design powerful drugs without unwanted side effects? Stanford University.  May 19, 2020.

https://phys.org/news/2020-05-powerful-drugs-unwanted-side-effects.html    

The << work could provide a framework for the rational design of drugs that are more effective and have fewer side effects. >>

Carl-Mikael Suomivuori, Naomi R. Latorraca, et al. Molecular mechanism of biased signaling in a prototypical G protein–coupled receptor. Science. 

Vol. 367, Issue 6480, pp. 881-887

doi: 10.1126/ science.aaz0326. Feb 21, 2020.

https://science.sciencemag.org/content/367/6480/881   

Also

keyword 'magic' in FonT

https://flashontrack.blogspot.com/search?q=magic

keyword 'GPCR'  in Wikipedia

https://en.m.wikipedia.org/wiki/G_protein-coupled_receptor

# behav: the smart sleep of flies (Drosophila melanogaster)

<< Flies that cannot take to the air respond by sleeping more as they learn to adapt to their flightlessness, (..) The findings, (..) suggest that sleep may be an evolutionary tool that helps animals adapt to challenging new situations. >>

<< Fruit flies' sleep looks a lot like people's. Baby flies need a lot of sleep, but as they get older, their need for sleep diminishes. Flies become more alert with caffeine and drowsier with antihistamines. And if you keep a fly awake one day, it will sleep more the next. >>

Flies sleep when need arises to adapt to new situations. Washington University School of Medicine. May 8, 2020.

https://phys.org/news/2020-05-flies-situations.html

K. Melnattur, B. Zhang, P. J. Shaw. Disrupting flight increases sleep and identifies a novel sleep-promoting pathway in Drosophila. Sci Adv 

Vol. 6, no. 19, eaaz2166. doi: 10.1126/sciadv.aaz2166. May 8, 2020.

https://advances.sciencemag.org/content/6/19/eaaz2166.full

Also

keyword 'Drosophila' in FonT

https://flashontrack.blogspot.com/search?q=drosophila

keyword 'mosca' in Notes (quasi- stochastic poetry)

https://inkpi.blogspot.com/search?q=mosca

# life: how humans could mutate, step by step, into proto- alien entities ...

AA << studied the brain after long-duration space flight. The authors performed serial MRI on 11 of 54 eligible International Space Station astronauts (10 men, one woman; five astronauts had previous exposure to spaceflight; mean mission duration almost 6 months), both preflight and at 1 week, 1 month, 3 months, 6 months, and 1 year after spaceflight. They found that prolonged microgravity exposure caused the following brain changes: (a) an approximate 2% expansion of brain and cerebral spinal fluid (CSF) volumes, attributable to both white matter and lateral ventricular measurements, and these remained elevated at 1-year after spaceflight, suggesting permanent alterations; (b) a 13% increase in mean CSF intraventricular (aqueductal) flow velocity, suggesting a reduction in intracranial compliance; and (c) in roughly half (six of 11 astronauts), depression of the pituitary dome compared with baseline (average midline height decreased from 5.9 to 5.3 mm), suggesting elevated intracranial pressure during spaceflight. >>

Michael H. Lev. The Long-term Effects of Spaceflight on Human Brain Physiology. Radiology. doi: 10.1148/radiol.2020201164. Apr 14, 2020.

https://pubs.rsna.org/doi/10.1148/radiol.2020201164

Chelsea Gohd. Space travel can seriously change your brain. Apr 14, 2020.

https://www.space.com/brain-changes-in-space-astronaut-health-study.html

# brain: related noise in perception, like a type of "groupthink"

<< The findings, (..) offer new insights into the limits of perception and could aid in the design of so-called neuroprosthetics-devices that enable people to regain some lost sensory capabilities. >>

<< because neurons are highly interconnected, when one randomly responds incorrectly and misidentifies an image, it can influence other neurons to make the same mistake. >>

<< You can think of correlated noise like a type of 'groupthink,' in which neurons can act like lemmings, with one heedlessly following another into making a mistake, >> Surya Ganguli

<< Remarkably, the visual system is able to cut through about 90% of this neuronal noise, but the remaining 10% places a limit on how finely we can discern between two images that look very similar. >>

<< With this study, we've helped resolve a puzzle that's been around for over 30 years about what limits mammals-and by extension humans-when it comes to sensory perception, >> Mark Schnitzer

Adam Hadhazy. Misfiring from jittery neurons sets fundamental limit on perception.  Stanford University. Apr 9, 2020.

https://medicalxpress.com/news/2020-04-misfiring-jittery-neurons-fundamental-limit.html

Rumyantsev OI, Lecoq JA, et al. Fundamental bounds on the fidelity of sensory cortical coding. Nature 580, 100–105 doi:.10.1038/ s41586-020-2130-2. Mar 18, 2020.

https://www.nature.com/articles/s41586-020-2130-2

# brain: lizard, an ancient dreamer (2)

<< Reptiles have a brain area previously suspected to play a role in mammalian higher cognitive processes, and establish its role in controlling brain dynamics in sleep. >>

<< The fact that we find a claustrum homolog in reptiles suggests that the claustrum is an ancient structure, likely present in the brains of the common vertebrate ancestor of reptiles and mammals, (..) While our results have not answered the question as to whether the claustrum plays a role in consciousness or higher cognitive functions, they indicate that it may play an important role in the control of brain states (such as in sleep), due to ascending input from the mid- and hindbrain, to its widespread projections to the forebrain and to its role in sharp-wave generation during slow-wave sleep, >> Gilles Laurent

Hidden away: An enigmatic mammalian brain area revealed in reptiles. Max Planck Society.  Feb 13, 2020

https://m.phys.org/news/2020-02-hidden-enigmatic-mammalian-brain-area.html

Hiroaki Norimoto, Lorenz A. Fenk, et al. A claustrum in reptiles and its role in slow-wave sleep. Nature volume 578, pages 413–418. Feb 12, 2020

https://www.nature.com/articles/s41586-020-1993-6

Also

keyword 'lizard' in FonT

https://flashontrack.blogspot.com/search?q=lizard

# brain: the memory switch p75NTR

<< many molecular and environmental factors have been studied to understand how synaptic plasticity is modulated. Sleep, as an evolutionary conserved biological function, has shown to be a critical player for the consolidation and filtering of synaptic circuitry underlying memory traces. Although sleep disturbances do not alter normal memory consolidation, they may reflect fundamental circuit malfunctions that can play a significant role in exacerbating diseases, such as autism and Alzheimer's disease. (..) This paper will review the role of the p75NTR (p75 neurotrophic receptor), critically discuss the impact and implications of this research as the bridge for sleep research and neurological diseases.>>

Shen Ning, Mehdi Jorfi. p75NTR as a Molecular Memory Switch.  arXiv: 1912.11449v1 [q-bio.NC]. Dec 24, 2019.

https://arxiv.org/abs/1912.11449

# brain AI bots: a hypothetical model for exploratory bots, the pulsating perceptions of mantis shrimps

AA << examined the neuronal organization of mantis shrimp, which are among the top predatory animals of coral reefs and other shallow warm water environments. >>

They << discovered a region of the mantis shrimp brain they called the reniform ("kidney-shaped") body. The discovery sheds new light on how the crustaceans may process and integrate visual information with other sensory input. >>

<< Mantis shrimp sport the most complex visual system of any living animal. They are unique in that they have a pair of eyes that move independently of each other, each with stereoscopic vision and possessing a band of photoreceptors that can distinguish up to 12 different wavelengths as well as linear and circular polarized light.  >>

<< One of the study's crucial findings was that neural connections link the reniform bodies to centers called mushroom bodies, iconic structures of arthropod brains that are required for olfactory learning and memory. >>

<< The fact that we were now able to demonstrate that the reniform body is also connected to the mushroom body and provides information to it, suggests that olfactory processing may take place in the context of already established visual memories, >> Nicholas Strausfeld.

How mantis shrimp make sense of the world. University of Arizona.  Nov 25, 2019. 

https://m.phys.org/news/2019-11-mantis-shrimp-world.html

Hanne Halkinrud Thoen, Gabriella Hannah Wolff, et al. The reniform body: An integrative lateral protocerebral neuropil complex of Eumalacostraca identified in Stomatopoda and Brachyura. Journal of Comparative Neurology. doi: 10.1002/cne.24788. Oct 16, 2019.

https://onlinelibrary.wiley.com/doi/abs/10.1002/cne.24788

FonT

these neural models could be reproduced for "compassionate" (or even "bonobos") bots, but NEVER for "nfulaw" purposes, please

keyword  "nfulaw" in FonT

https://flashontrack.blogspot.com/search?q=nfulaw

# brain: the flexible mental maps of flies

<< In the Drosophila brain, 'compass'  neurons track the orientation of the body and head (the fly’s heading) during navigation >>

<<  a visual cue can evoke synaptic inhibition in compass neurons and that R (ring) neurons mediate this inhibition. Each compass neuron is inhibited only by specific visual cue positions, indicating that many potential connections from R neurons onto compass neurons are actually weak or silent. (..) the pattern of visually evoked inhibition can reorganize over minutes as the fly explores an altered virtual-reality environment. >>

Yvette E. Fisher, Jenny Lu, et al. Sensorimotor experience remaps visual input to a heading-direction network.  Nature. doi: 10.1038/s41586-019-1772-4. Nov 20, 2019. 

https://www.nature.com/articles/s41586-019-1772-4

To navigate, flies make flexible mental maps of the world. Howard Hughes Medical Institute. Nov 20, 2019.

https://m.phys.org/news/2019-11-flies-flexible-mental-world.html

Also

<<  Considerando invece l' immagine classica della "mosca nella bottiglia", >>  in: 2066 - voli a casaccio. Notes. Oct 01, 2006. 

https://inkpi.blogspot.com/2006/10/2066-voli-casaccio.html

# brain: to test schizophrenia in human hair.

<< MPST gene expression (which leads to hydrogen sulphide production) was higher in postmortem brains from people with schizophrenia than in those from unaffected people. MPST protein levels in these brains also correlated well with the severity of premortem symptoms.  >>

AA << examined hair follicles from more than 150 people with schizophrenia and found that expression of MPST mRNA was much higher than people without schizophrenia. Even though the results were not perfect-indicating that sulfide stress does not account for all cases of schizophrenia-MPST levels in hair could be a good biomarker for schizophrenia before other symptoms appear. >>

<< Nobody has ever thought about a causal link between hydrogen sulfide and schizophrenia, (..) Once we discovered this, we had to figure out how it happens and if these findings in mice would hold true for people with schizophrenia. >> Takeo Toshikawa.

Biomarker for schizophrenia can be detected in human hair. Riken. Oct 28, 2019.

https://medicalxpress.com/news/2019-10-biomarker-schizophrenia-human-hair.html

Masayuki Ide, Tetsuo Ohnishi, et al. 

Excess hydrogen sulfide and polysulfides production underlies a schizophrenia pathophysiology. EMBO Mol Med (2019) e10695. doi: 10.15252/emmm.201910695. Oct 28, 2019.

https://www.embopress.org/doi/full/10.15252/emmm.201910695   

# brain: the 'loosely balanced state' of cerebral cortex

<< Many studies have shown that the excitation and inhibition received by cortical neurons remain roughly balanced across many conditions. A key question for understanding the dynamical regime of cortex is the nature of this balancing. (..) loose balance, but not tight balance, can yield many nonlinear population behaviors seen in sensory cortical neurons, allow the presence of correlated variability, and yield decrease of that variability with increasing external stimulus drive as observed across multiple cortical areas. >>  

<< at least sensory, and perhaps all of, cortex operates in a regime in which the inhibition and excitation neurons receive are loosely balanced. This along with the supralinear input/output function of individual neurons and simple assumptions on connectivity explains a large set of cortical response properties. A key outstanding question is the computational function or functions of this loosely balanced state and the response properties it creates >>

Yashar Ahmadian, Kenneth D. Miller.  What is the dynamical regime of cerebral cortex?  arXiv:1908.10101v2 [q-bio.NC] Aug 28, 2019.   

https://arxiv.org/abs/1908.10101  

# brain: to trace transitions from consciousness to unconscious subliminal perception

AA << study the transition in the functional networks that characterize the human brains’ conscious-state to an unconscious subliminal state of perception >>

<< the most inner core (i.e., the most connected kernel) of the conscious-state functional network corresponds to areas which remain functionally active when the brain transitions from the conscious-state to the subliminal-state. That is, the inner core of the conscious network coincides with the subliminal-state. >>

<< This finding imposes constraints to theoretical models of consciousness, in that the location of the core of the functional brain network is in the unconscious part of the brain rather than in the conscious state as previously thought. >>

Francesca Arese Lucini, Gino Del Ferraro, et al. How the Brain Transitions from Conscious to Subliminal Perception. Neuroscience. Volume 411, Jul 15, 2019, Pages 280-290.

https://www.sciencedirect.com/science/article/abs/pii/S0306452219302052

<< The k-core of the conscious state is reduced to three active regions of the brain, the fusiform gyrus (left and right) and the precentral gyrus. These regions are the only active in the subliminal state. >>

Physicists use mathematics to trace neuro transitions. City College of New York. Jul 18, 2019.

https://m.medicalxpress.com/news/2019-07-physicists-mathematics-neuro-transitions.html