Discovery of Silent Synapses May explain and Provide brain Plasticity in Adulthood

Amazing stuff! This could be a huge discovery!

"... Silent synapses are otherwise complete neuronal connections that lack a key signaling protein—AMPA receptors—that renders them inactive. They were thought to be unique to early development, as previous work found that the silent connections vanish by the time a mouse has reached adulthood. But researchers may have been looking in the wrong place. In young animals, silent synapses are formed from larger protrusions called dendritic spines. But in adults, they can be found on the ends of threadlike structures called filopodia, according to the new study. ..."

From the abstract:

"Newly generated excitatory synapses in the mammalian cortex lack sufficient AMPA-type glutamate receptors to mediate neurotransmission, resulting in functionally silent synapses that require activity-dependent plasticity to mature. Silent synapses are abundant in early development, during which they mediate circuit formation and refinement, but they are thought to be scarce in adulthood. However, adults retain a capacity for neural plasticity and flexible learning that suggests that the formation of new connections is still prevalent. Here we used super-resolution protein imaging to visualize synaptic proteins at 2,234 synapses from layer 5 pyramidal neurons in the primary visual cortex of adult mice. Unexpectedly, about 25% of these synapses lack AMPA receptors. These putative silent synapses were located at the tips of thin dendritic protrusions, known as filopodia, which were more abundant by an order of magnitude than previously believed (comprising about 30% of all dendritic protrusions). Physiological experiments revealed that filopodia do indeed lack AMPA-receptor-mediated transmission, but they exhibit NMDA-receptor-mediated synaptic transmission. We further showed that functionally silent synapses on filopodia can be unsilenced through Hebbian plasticity, recruiting new active connections into a neuron’s input matrix. These results challenge the model that functional connectivity is largely fixed in the adult cortex and demonstrate a new mechanism for flexible control of synaptic wiring that expands the learning capabilities of the mature brain."

Silent Synapses May Provide Plasticity in Adulthood | The Scientist Magazine® Inactive synapses—found on tiny neuronal projections called filopodia—are abundant in the adult brain, a mouse study suggests.

Filopodia are a structural substrate for silent synapses in adult neocortex (no public access, but article above contains link to PDF file)

Discovery of an extra fourth layer lining the human brain

Amazing stuff! 

We still do not know even our brains very well but many demagogues want us to believe on a daily basis we can predict climate change up to the year 2100!

"An extra layer lines the brain

The traditional view is that the brain is surrounded by three layers, the dura, arachnoid, and pia mater. Møllgård et al. found a fourth meningeal layer called the subarachnoid lymphatic-like membrane (SLYM). SLYM is immunophenotypically distinct from the other meningeal layers in the human and mouse brain and represents a tight barrier for solutes of more than 3 kilodaltons, effectively subdividing the subarachnoid space into two different compartments. SLYM is the host for a large population of myeloid cells, the number of which increases in response to inflammation and aging, so this layer represents an innate immune niche ideally positioned to surveil the cerebrospinal fluid."

From the abstract:

"The central nervous system is lined by meninges, classically known as dura, arachnoid, and pia mater. We show the existence of a fourth meningeal layer that compartmentalizes the subarachnoid space in the mouse and human brain, designated the subarachnoid lymphatic-like membrane (SLYM). SLYM is morpho- and immunophenotypically similar to the mesothelial membrane lining of peripheral organs and body cavities, and it encases blood vessels and harbors immune cells. Functionally, the close apposition of SLYM with the endothelial lining of the meningeal venous sinus permits direct exchange of small solutes between cerebrospinal fluid and venous blood, thus representing the mouse equivalent of the arachnoid granulations. The functional characterization of SLYM provides fundamental insights into brain immune barriers and fluid transport."

A mesothelium divides the subarachnoid space into functional compartments | Science (no public access)

Babies spend most of their time asleep. New technologies are beginning to reveal why

Amazing stuff!

"... “This is a time when … the brain is developing new connections at a rate of something like a million synapses a second,” ...

Eight ways scientists are unwrapping the mysteries of the human brain

Optogenetics and advanced imaging have helped neuroscientists understand how memories form and made it possible to manipulate them. ...

The team has used a cap with light sources and sensors embedded in it. Together, these components can measure blood flow in the brain in the same way as a pulse oximeter clipped onto your finger in a doctor’s office. ...
The new device makes use of recently developed tiles that each contain several light sources and detectors. ... team has fitted 12 of these tiles into a cap suitable for newborns, connected to a computer with a single cable. The resulting system offers an image of the brain “at least 10 times the resolution of the [previous] fiber-optic cable system,” ...

Babies cycle through two phases of sleep: an active phase, which is accompanied by twitching and grimacing, is followed by a quiet phase, when the baby is very still. ...

Later, when ... team analyzed snapshots of the recordings, they noticed differences in the brain during active and quiet sleep. During active sleep, when the babies were more fidgety, brain regions in the left and right hemispheres seemed to fire at the same time, in the same way. This hints that new, long connections are forming all the way across the brain ... During quiet sleep, it looks as though more short connections are forming within brain regions. ... "

Babies spend most of their time asleep. New technologies are beginning to reveal why | MIT Technology Review Monitoring the brains of newborn babies while they sleep gives us insight into how they learn.

Are brain implants the future of computing?

Recommendable!

Silent synapses are abundant in the adult brain allowing learn like an adolescent into late age

Good news! This could be a major game changer! 

Another nice example, where the majority of scientists has been dead wrong for decades! Soon, we will probably learn that the so called settled science on Global Warming/Climate Change shares the same fate! 😊

"... neuroscientists have discovered that the adult brain contains millions of “silent synapses” — immature connections between neurons that remain inactive until they’re recruited to help form new memories.

Until now, it was believed that silent synapses were present only during early development, when they help the brain learn the new information that it’s exposed to early in life. However, the new ... study revealed that in adult mice, about 30 percent of all synapses in the brain’s cortex are silent.

The existence of these silent synapses may help to explain how the adult brain is able to continually form new memories and learn new things without having to modify existing conventional synapses, the researchers say. ...

When scientists first discovered silent synapses decades ago, they were seen primarily in the brains of young mice and other animals. During early development, these synapses are believed to help the brain acquire the massive amounts of information that babies need to learn about their environment and how to interact with it. In mice, these synapses were believed to disappear by about 12 days of age (equivalent to the first months of human life). ..."

From the abstract:

"Newly generated excitatory synapses in the mammalian cortex lack sufficient AMPA-type glutamate receptors to mediate neurotransmission, resulting in functionally silent synapses that require activity-dependent plasticity to mature. Silent synapses are abundant in early development, during which they mediate circuit formation and refinement, but they are thought to be scarce in adulthood. However, adults retain a capacity for neural plasticity and flexible learning that suggests that the formation of new connections is still prevalent. Here we used super-resolution protein imaging to visualize synaptic proteins at 2,234 synapses from layer 5 pyramidal neurons in the primary visual cortex of adult mice. Unexpectedly, about 25% of these synapses lack AMPA receptors. These putative silent synapses were located at the tips of thin dendritic protrusions, known as filopodia, which were more abundant by an order of magnitude than previously believed (comprising about 30% of all dendritic protrusions). Physiological experiments revealed that filopodia do indeed lack AMPA-receptor-mediated transmission, but they exhibit NMDA-receptor-mediated synaptic transmission. We further showed that functionally silent synapses on filopodia can be unsilenced through Hebbian plasticity, recruiting new active connections into a neuron’s input matrix. These results challenge the model that functional connectivity is largely fixed in the adult cortex and demonstrate a new mechanism for flexible control of synaptic wiring that expands the learning capabilities of the mature brain."

Silent synapses are abundant in the adult brain | MIT News | Massachusetts Institute of Technology These immature connections may explain how the adult brain is able to form new memories and absorb new information.

Filopodia are a structural substrate for silent synapses in adult neocortex (no public access)

Researchers have discovered that the adult mouse brain contains millions of silent synapses, located on tiny structures called filopodia.

Fig. 1: Filopodia account for a large fraction of dendritic protrusions in L5 and L2/3 pyramidal neurons of adult mouse primary visual cortex.

Mapping the whole human brain: Allen Institute to lead global collaboration

Good news! Very exciting! Exploration and discovery at its best! The human brain is still largely terra incognita!

Thanks to the generosity and philanthropy of the co-founder of Microsoft Paul Allen!

"Scientists at the Allen Institute are launching the brain equivalent of the Human Genome Project, leading a new global collaboration to map the approximately 200 billion cells in the human brain by their type and function.  ...
The collaboration is funded by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative as part of The BRAIN Initiative Cell Atlas Network, or BICAN, and will also build detailed atlases of macaque and marmoset brains. ... the human and primate atlas grant project also includes sub-projects led by researchers from 17 other institutions in the U.S., Europe and Japan. ..."

Mapping the whole human brain: Allen Institute to lead global collaboration NIH BRAIN Initiative to fund primate brain atlases, maps of developing mouse brain, coordination and knowledge sharing, and brain function research

Human brain cell type diversity in the primary motor cortex, the region of the brain that controls movement. These data were generated using a technique known as single-cell transcriptomics to capture the full suite of genes switched on in each brain cell.

Did this gene give modern human brains their edge?

Amazing stuff!

"More than 500,000 years ago, the ancestors of Neanderthals and modern humans were migrating around the world when a fateful genetic mutation caused some of their brains to suddenly improve. This mutation ... dramatically increased the number of brain cells in the hominins that preceded modern humans, probably giving them a cognitive advantage over their Neanderthal cousins. ..."

"... Pinson et al. report that expression of a variant of human transketolase-like protein 1 (TKTL1) increases the number of bRGs in modern humans and thereby the output of upper layer projection neurons. This genetic change could contribute to differences in cognition with extinct archaic humans."

From the abstract:

"Neanderthal brains were similar in size to those of modern humans. We sought to investigate potential differences in neurogenesis during neocortex development. Modern human transketolase-like 1 (TKTL1) differs from Neanderthal TKTL1 by a lysine-to-arginine amino acid substitution. Using overexpression in developing mouse and ferret neocortex, knockout in fetal human neocortical tissue, and genome-edited cerebral organoids, we found that the modern human variant, hTKTL1, but not the Neanderthal variant, increases the abundance of basal radial glia (bRG) but not that of intermediate progenitors (bIPs). bRG generate more neocortical neurons than bIPs. The hTKTL1 effect requires the pentose phosphate pathway and fatty acid synthesis. Inhibition of these metabolic pathways reduces bRG abundance in fetal human neocortical tissue. Our data suggest that neocortical neurogenesis in modern humans differs from that in Neanderthals."

Did this gene give modern human brains their edge? A mutation present in modern humans seems to drive greater neuron growth than does an ancient hominin version.

Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals (no public access)

Scaling brain neurogenesis across evolution (no public access) A genetic change could explain increased cortical neurogenesis in modern humans

Early Humans' Brains Were More Apelike than Modern

Very recommendable! The long held belief that the first hominids to leave Africa were intelligent and had a large brain was too nice! Of course, Homo erectus (the upright hominin) must have had a rather modern brain!

Even today, human brains still seem primitive! How else can you e.g. explain the highly irrational, extreme, and very long lasting global overreaction to the fairly harmless SARS-Cov-2 virus? Pardon, my sarcasm!

"... Here, we show that the brains of early Homo from Africa and Western Asia (Dmanisi) retained a primitive, great ape–like organization of the frontal lobe. By contrast, African Homo younger than 1.5 million years ago, as well as all Southeast Asian Homo erectus, exhibited a more derived, humanlike brain organization. Frontal lobe reorganization, once considered a hallmark of earliest Homo in Africa, thus evolved comparatively late, and long after Homo first dispersed from Africa. ..."

Early Humans' Brains Were More Apelike than Modern | The Scientist Magazine® Impressions that ancient brains left in fossilized skulls reveal that the first human ancestors to migrate out of Africa had much more primitive brains than previously thought.

Here is the link to the underlying research article:

The primitive brain of early Homo (open access)

Creativity Emerges from Spontaneous Neural Activity

Very recommendable!

"... Around 20 years ago, ... pioneered research into the phenomenon of spontaneously emerging resting-state fluctuations – very slow fluctuations of neuronal activity that occur subconsciously and that are distinguishable from the bursts of activity that occur when conscious events take place. ... while their brains were scanned with functional magnetic resonance imaging (fMRI). Each time one of the participants came up with a creative idea, the researchers noted that the reporting of that idea was preceded by slow electrical activity that was highly reminiscent of slowly rising resting-state fluctuations. ... There was a significant correlation between the spontaneous, resting-state fluctuations and the slow activity that preceded the moment of a creative idea appearing. ..."

"These results suggest a common function of resting-state fluctuations as the neural mechanism underlying the generation of free and creative behaviors in the human cortex."

Creativity Emerges from Spontaneous Neural Activity Researchers at the Weizmann Institute of Science now propose an explanation for these mysterious moments of inspiration that pop up from the depths of our unconsciousness. The researchers ... found that spontaneous waves of brain activity – also called resting-state fluctuations – are the origins of this amazing, yet poorly understood, human ability; and they propose that these fluctuations are a universal mechanism underlying creativity.

Here is the prospective research article:

Resting-State Fluctuations Underlie Free and Creative Verbal Behaviors in the Human Brain | Cerebral Cortex | Oxford Academic