Discovery of new pathways controlling the serotonergic system

With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific journal Neuron, may lead to new knowledge on a number of psychiatric conditions and the development of new pharmaceuticals.

The neurotransmitter serotonin controls impulsivity, mood and our cognitive functions, among other things, and comes from the serotonergic neurons – the neurons that produce serotonin. So that we have good mental health and normal behaviour, it is important that there is correctly regulated activity among these neurons. The activity is governed by other neurons from different regions of the brain via direct links, known as synapses, on the serotonergic neurons. Imbalance in the serotonergic system can lead to depression, Parkinson’s disease, schizophrenia and autism, among other things.

So far it has been impossible to study in detail how different types of nerve cells are interlinked and how the brain’s networks control behaviour. Consequently, there has also been a lack of knowledge of which nerve cells control the activity of the serotonergic neurons. But with the help of new methods, researchers at Karolinska Institutet can now investigate how the various networks of the brain are organised and how they work. The research team, led by Konstantinos Meletis of the Department of Neuroscience, has established which networks of the brain control the serotonergic neurons.

“We have been able to create a new type of map of the neurons’ contacts and discovered new pathways that control the serotonergic system. These networks were previously unknown and are very interesting in terms of how they help us to understand how the serotonergic system works, which could also help us to understand certain mental illnesses,” Konstantinos Meletis explains.

In order to map out which neurons have direct contact with serotonergic neurons, the researchers established a method in which these cells were marked with a rabies virus which produced a fluorescent marker. Via genetic manipulation, the rabies virus was then spread to all of the neurons directly linked to the serotonergic neurons. The researchers thereby gained a very detailed, three-dimensional image of the networks of the brain that control serotonin. Using optogenetics, a method in which light is used to control the activity of neurons, the researchers were then able to manipulate select networks and thus study their effect on the serotonergic neurons.

Via mapping, the researchers discovered a network in the frontal lobe which is associated with cognition and well-being and which controls the serotonergic neurons. Researchers also found that serotonin can be controlled from new types of neurons in the basal ganglia, an area of the cerebrum which among other things controls movement, well-being and decision-making; a discovery which may have significance for conditions such as Parkinson’s disease.

“We are very optimistic that the revolution we are now seeing in brain research could also lead to entirely new and effective medicine in the field of psychiatry,” Konstantinos Meletis explains.

(Image caption: Part of a brain slice in which a transplanted induced neural stem cell is fully integrated in the neuronal network of the brain (blue) to develop into a complex and functional neuron.)

Implanted Neurons become Part of the Brain

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have grafted neurons reprogrammed from skin cells into the brains of mice for the first time with long-term stability. Six months after implantation, the neurons had become fully functionally integrated into the brain. This successful, because lastingly stable, implantation of neurons raises hope for future therapies that will replace sick neurons with healthy ones in the brains of Parkinson’s disease patients, for example. The Luxembourg researchers published their results in the current issue of ‘Stem Cell Reports’.

The LCSB research group around Prof. Dr. Jens Schwamborn and Kathrin Hemmer is working continuously to bring cell replacement therapy to maturity as a treatment for neurodegenerative diseases. Sick and dead neurons in the brain can be replaced with new cells. This could one day cure disorders such as Parkinson’s disease. The path towards successful therapy in humans, however, is long. “Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future. Our research results have taken us a step further in this direction,” declares stem cell researcher Prof. Schwamborn, who heads a group of 15 scientists at LCSB.

In their latest tests, the research group and colleagues from the Max Planck Institute and the University Hospital Münster and the University of Bielefeld succeeded in creating stable nerve tissue in the brain from neurons that had been reprogrammed from skin cells. The stem cell researchers’ technique of producing neurons, or more specifically induced neuronal stem cells (iNSC), in a petri dish from the host’s own skin cells considerably improves the compatibility of the implanted cells. The treated mice showed no adverse side effects even six months after implantation into the hippocampus and cortex regions of the brain. In fact it was quite the opposite – the implanted neurons were fully integrated into the complex network of the brain. The neurons exhibited normal activity and were connected to the original brain cells via newly formed synapses, the contact points between nerve cells.

The tests demonstrate that the scientists are continually gaining a better understanding of how to treat such cells in order to successfully replace damaged or dead tissue. “Building upon the current insights, we will now be looking specifically at the type of neurons that die off in the brain of Parkinson’s patients – namely the dopamine-producing neurons,” Schwamborn reports. In future, implanted neurons could produce the lacking dopamine directly in the patient’s brain and transport it to the appropriate sites. This could result in an actual cure, as has so far been impossible. The first trials in mice are in progress at the LCSB laboratories on the university campus Belval.

Making sense of scents

For many animals, making sense of the clutter of sensory stimuli is often a matter or literal life or death.

Exactly how animals separate objects of interest, such as food sources or the scent of predators, from background information, however, remains largely unknown. Even the extent to which animals can make such distinctions, and how differences between scents might affect the process were largely a mystery – until now.

A new study, described in an August 3 paper in Nature Neuroscience, a team of researchers led by Venkatesh Murthy, Professor of Molecular and Cellular Biology, showed that while mice can be trained to detect specific odorants embedded in random mixtures, their performance drops steadily with increasing background components. The team included Dan Rokni, Vikrant Kapoor and Vivian Hemmelder, all from Harvard University.

"There is a continuous stream of information constantly arriving at our senses, coming from many different sources," Murthy said. "The classic example would be a cocktail party – though it may be noisy, and there may be many people talking, we are able to focus our attention on one person, while ignoring the background noise.

"Is the same also true for smells?" he continued. "We are bombarded with many smells all jumbled up. Can we pick out one smell "object" – the smell of jasmine, for example, amidst a riot of other smells? Our experience tells us indeed we can, but how do we pick out the ones that we need to pay attention to, and what are the limitations?"

To find answers to those, and other, questions, Murthy and colleagues turned to mice.

After training mice to detect specific scents, researchers presented the animals with a combination of smells – sometimes including the “target” scent, sometimes not. Though previous studies had suggested animals are poor at individual smells, and instead perceived the mixture as a single smell, their findings showed that mice were able to identify when a target scent was present with 85 percent accuracy or better.

"Although the mice do well overall, they perform progressively poorer when the number of background odors increases," Murthy explained.

Understanding why, however, meant first overcoming a problem particular to olfaction.

While the relationship between visual stimuli is relatively easy to understand – differences in color can be easily described as differences in the wavelength of light – no such system exists to describe how two odors relate to each other. Instead, the researchers sought to describe scents according to how they activated neurons in the brain.

Using fluorescent proteins, they created images that show how each of 14 different odors stimulated neurons in the olfactory bulb. What they found, Murthy said, was that the ability of mice to identify a particular smell was markedly diminished if background smells activated the same neurons as the target odor.

"Each odor gives rise to a particular spatial pattern of neural responses," Murthy said. "When the spatial pattern of the background odors overlapped with the target odor, the mice did much more poorly at detecting the target. Therefore, the difficulty of picking out a particular smell among a jumble of other odors, depends on how much the background interferes with your target smell. So, we were able to give a neural explanation for how well you can solve the cocktail party problem.

"This study is interesting because it first shows that smells are not always perceived as one whole object – they can be broken down into their pieces," he added. "This is perhaps not a surprise – there are in fact coffee or wine specialists that can detect faint whiffs of particular elements within the complex mixture of flavors in each coffee or wine. But by doing these studies in mice, we can now get a better understanding of how the brain does this. One can also imagine that understanding how this is done may also allow us to build artificial olfactory systems that can detect specific chemicals in the air that are buried amidst a plethora of other odors."

Clues to curbing obesity found in neuronal ‘sweet spot’

Preventing weight gain, obesity, and ultimately diabetes could be as simple as keeping a nuclear receptor from being activated in a small part of the brain, according to a new study by Yale School of Medicine researchers.

Published in the Aug. 1 issue of The Journal of Clinical Investigation (JCI), the study showed that when the researchers blocked the effects of the nuclear receptor PPARgamma in a small number of brain cells in mice, the animals ate less and became resistant to a high-fat diet.

“These animals ate fat and sugar, and did not gain weight, while their control littermates did,” said lead author Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. “We showed that the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity.”

POMC neurons are found in the hypothalamus and regulate food intake. They are the neurons that when activated make you feel full and curb appetite. PPARgamma regulates the activation of these neurons.

Diano and her team studied transgenic mice that were genetically engineered to delete the PPARgamma receptor from POMC neurons. They wanted to see if they could prevent the obesity associated with a high-fat, high-sugar diet.

“When we blocked PPARgamma in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active,” said Diano, who is also professor of comparative medicine and neurobiology at Yale and director of the Reproductive Neurosciences Group.

The findings also have key implications in diabetes. PPARgamma is a target of thiazolidinedione (TZD), a class of drugs used to treat type 2 diabetes. They lower blood-glucose levels, however, patients gain weight on these medications.

“Our study suggests that the increased weight gain in diabetic patients treated with TZD could be due to the effect of this drug in the brain, therefore, targeting peripheral PPARgamma to treat type 2 diabetes should be done by developing TZD compounds that can’t penetrate the brain,” said Diano. “We could keep the benefits of TZD without the side-effects of weight gain. Our next steps in this research are to test this theory in diabetes mouse models.”

(Figure 1: Axons grow and turn in response to guidance cues (arrows), which regulate endocytosis and exocytosis at the tips of growing axons. Credit: © 2014 T. Tojima et al.)

Steering the filaments of the developing brain

During brain development, nerve fibers grow and extend to form brain circuits. This growth is guided by molecular cues (Fig. 1), but exactly how these cues guide axon extension has been unclear. Takuro Tojima and colleagues from the RIKEN Brain Science Institute have now uncovered the signaling pathways responsible for turning growing nerve fibers, or axons, toward or away from guidance cues.

The researchers previously showed that axon-repelling cues act by inducing the removal of cell membrane—a process called endocytosis—from the side of the axon closest to the repulsive cue. The enzyme PIPKIγ90 is known to be involved in endocytosis in axons during certain types of synaptic activity, so the researchers investigated whether PIPKIγ90 also played a role in endocytosis during axon turning. By examining the developing brains of chicken embryos expressing an inactive form of PIPKIγ90, the researchers found that cues normally inducing endocytosis were no longer effective in repelling axon growth.

Cues that normally attract axons do so by driving membrane addition—exocytosis—on the side of the axon closest to the cue and also by suppressing endocytosis. Tojima’s team found that axons continued to be attracted to such cues even in the absence of PIPKIγ90, suggesting that PIPKIγ90 signaling is not involved in axon attraction.

The activity of PIPKIγ90 is known to be regulated by an enzyme called CDK5, a subunit of which binds to the protein kinase CaMKII. The researchers found that by inhibiting CDK5 or CaMKII, and thereby blocking the regulation of PIPKIγ90 that is needed to suppress endocytosis, endocytosis could occur in response to attractive cues.

They also found, however, that blocking CDK5 or CaMKII did not have any effect on endocytosis if the neurons expressed a mutant version of PIPKIγ90 that was unaffected by CDK5 and CaMKII signaling. As inhibitors of CDK5 or CaMKII did not alter endocytosis in response to repulsive cues, the team’s findings indicate that different signaling pathways are responsible for turning axons toward or away from guidance cues.

Additionally, Tojima and his colleagues showed that they could induce the attraction of axons toward drugs that inhibit endocytosis, suggesting that being able to control the direction of axon growth has potential therapeutic applications. “We hope our findings will aid in the development of future therapeutic strategies for rewiring neuronal networks after spinal cord injury and neurodegenerative diseases,” explains Tojima.

Watching neurons fire from a front-row seat

They are with us every moment of every day, controlling every action we make, from the breath we breathe to the words we speak, and yet there is still a lot we don’t know about the cells that make up our nervous systems. When things go awry and nerve cells don’t communicate as they should, the consequences can be devastating. Speech can be slurred, muscles stop working on command and memories can be lost forever.

Better understanding of how neurons and brains work could lead to new prevention, diagnostic and treatment techniques, but the brain is complex and difficult to study. If you were to hold your brain, you would likely marvel at how much it feels and moves like Jell-O. This tissue is composed of neurons and other supporting cells with tiny cell bodies, which generate electrical signals that determine how the brain and the nervous system function.

Those signals can be recorded and measured if a suitably small electrode is in the vicinity, but that presents challenges. Brain tissue is always moving in response to the body’s movement and breathing patterns. In addition, the nerve tissue is incredibly sensitive. If disrupted by a foreign body, the cells trigger an immune response to encapsulate the intruder and barricade it from the electrical signal it’s trying to capture and understand.

Working to develop intelligent neural interfaces

That challenge led Jit Muthuswamy, an associate professor of biomedical engineering at Arizona State University, Tempe (ASU), to pursue a robotic electrode system that would seek and maintain contact with neurons of interest autonomously in a subject going through normal behavioral routines. That led him to Sandia National Laboratories.

“We are working to develop chronic, reliable, intelligent neural interfaces that will communicate with single neurons in a variety of applications, some of which are emerging and others that are closer to market,” Muthuswamy said. “Applications like brain prostheses are critically dependent on us being able to interface and communicate with single neurons reliably over the course of a patient’s life. Such reliable neural interfaces are also critical to help us understand the dynamic changes in the wiring diagram of the brain.”

Key to the success of that robotic approach are the microscale actuators needed to reposition the electrodes. This led Muthuswamy in 2000 to seek out Sandia engineer Murat Okandan and the unique microsystems engineering capabilities available at Sandia’s Microsystems and Engineering Sciences Applications facility.

“The process flow we use to make these isn’t available anywhere else in the world, so the level of complexity and mechanical design space we had to design and fabricate these was immensely larger than what other researchers might have,” Okandan said. He has been working with Muthuswamy’s research team since that initial contact to find a suitable method to track individual neurons as they fire.

Earlier probes were made of a sharpened metal wire inserted in the tissue. The closer the probe is to the neuron, the stronger the signal, so experimenters ideally try to get as close as possible without disrupting surrounding tissue. The problem is that even a thin wire is too big; such a probe can take measurements around the neuron, but is far too cumbersome to be reliable over time.

Equally important is capturing the signals from an awake animal. Given their size and rigidity, current probes aren’t suited to gather recordings as the animal responds to its environment. Those units aren’t self-contained, so they keep the animals from moving around freely.

Microscale key to capturing signals from awake, moving animals

Microscale actuators and microelectrodes are critical to addressing both of those issues so probes can interact with individual nerve cells while doing minimal damage to surrounding tissue. The microscale actuators and associated packaging system developed at ASU and Sandia let a probe move autonomously in and out of the areas surrounding the cell, collecting measurements while compensating for any movement in the neuron or brain tissue.

About the size of a thumbnail, the self-contained unit has three microelectrodes and associated micro actuators. When a current runs through the thermal actuator, it expands and pushes the microelectrodes outward over the edge of the unit, which is flat to fit against the tissue. Because the actuator is so small, it can be heated to several hundred degrees Celsius and cooled again 1,000 times per second. It takes 540 cycles to fully extend the probe, but that can be done quickly – in a second or less.

The probes were implanted in the somatosensory cortex of rodents and rigorously tested in numerous experiments, both in acute and long-term conditions, Muthuswamy said. Animal procedures were carried out with the approval of ASU’s Institute of Animal Care and Use Committee, and experiments were done in accordance with National Institute of Health guidelines.

Muthuswamy said the neural probes demonstrated significant improvement in the quality and reliability of the signals when the probes were moved with precision using the Sandia microactuators in response to loss of neural signals. Further, he said, adding autonomous closed-loop controls to compensate for microscale perturbations in brain tissue significantly improved the stability of neural recordings from the brain.

Scale of this system is unique

Thermal actuators have been used for years at Sandia and elsewhere, but the scale of this system is unique. “The idea that we could build this system to achieve multiple millimeters of total displacement out of a micron-scaled device was a significant milestone,” said Sandia engineer Michael Baker, who designed the actuator. “We used electrostatic actuators in the past, but the thermal actuator provides much higher force, which is needed to move the probe in tissue.”

The microelectrodes are made of highly conductive polysilicon, which the team discovered has a number of advantages. It is almost metal-like in its conductivity, but durable enough for millions of cycles. It provides a signal-to-noise ratio much greater than previous wire probes and provides high-quality measurement signals.

Muthuswamy and Okandan currently are seeking to produce richer data with resolution in the submicron range to be able to go inside cells and take measurements there. They also are working on stacking the existing neural probe chips and decreasing the spaces between probes. Muthuswamy’s Neural Microsystems lab at ASU has developed a unique stacking approach for creating three-dimensional arrays of actuated microelectrodes.

“By building a three-dimensional array, we would have access to significantly more information, rather than just a slice,” Okandan said. “We’re very encouraged by the progress we have made, and are looking forward to building on that progress.”

Study Suggests Disruptive Effects of Anesthesia on Brain Cell Connections Are Temporary

A study of juvenile rat brain cells suggests that the effects of a commonly used anesthetic drug on the connections between brain cells are temporary.

The study, published in this week’s issue of the journal PLOS ONE, was conducted by biologists at the University of California, San Diego and Weill Cornell Medical College in New York in response to concerns, arising from multiple studies on humans over the past decade, that exposing children to general anesthetics may increase their susceptibility to long-term cognitive and behavioral deficits, such as learning disabilities.

An estimated six million children, including 1.5 million infants, undergo surgery in the United States requiring general anesthesia each year and a least two large-scale clinical studies are now underway to determine the potential risks to children and adults.

“Since these procedures are unavoidable in most cases, it’s important to understand the mechanisms associated with the potentially toxic effects of anesthetics on the developing brain, and on the adult brain as well,” said Shelley Halpain, a professor of biology at UC San Diego and the Sanford Consortium for Regenerative Medicine, who co-headed the investigation. “Because the clinical studies haven’t been completed, preclinical studies, such as ours, are needed to define the effects of various anesthetics on brain structure and function.”

“There is concern now about cognitive dysfunction from surgery and anesthesia—how much these effects are either permanent or slowly reversible is very controversial,” said Hugh Hemmings, Jr., chair of anesthesiology at Weill Cornell and the study’s other senior author. “It has been suggested recently that some of the effects of anesthesia may be more lasting than previously thought. It is not clear whether the residual effects after an operation are due to the surgery itself, or the hospitalization and attendant trauma, medications and stress—or a combination of these issues.”

However, he added, “There is evidence that some of the delayed or persistent cognitive effects after surgery are not primarily due to anesthesia itself, but more importantly to brain inflammation resulting from the surgery. But this is not yet clear.”

The team of biologists examined one of the most commonly used general anesthetics, a derivative of ether called “isoflurane” used to maintain anesthesia during surgery.

“Previous studies in cultured neurons and in the intact brains of rodents provided evidence suggesting that exposure to anesthetics might render neurons more susceptible to cell death through a process called ‘apoptosis’,” said Halpain. “While overt cell death could certainly be one way to explain any long-lasting neurocognitive consequences of general anesthesia, we hypothesized that there could be other cellular mechanisms that disrupt neural circuits without inducing cell death per se.”

One such mechanism, she added, is known as “synaptotoxicity.” In this mechanism of neural-circuit disruption, the “synapses,” or junctions between neurons, become weakened or shrink away due to some factor that injures the neurons locally along their axons (the long processes of neurons that transmit signals) and dendrites (the threadlike extensions of neurons that receive nerve signals) without inducing the neurons themselves to die.

In the experiments at UC San Diego headed by Jimcy Platholi, a postdoctoral researcher in Halpain’s lab who is now at Weill Cornell, the scientists used neurons from embryonic rats taken from the hippocampus, a part of the mammalian forebrain essential for encoding newly acquired memories and ensuring that short-term memories are converted into long-term memories. The researchers cultured these brain cells in a laboratory dish for three weeks, allowing the neurons time to mature and to develop a dense network of synaptic connections and “dendritic spines”—specialized structures that protrude from the dendrites and are essential mediators of activity throughout neural networks.

“Evidence from animal studies indicates that new dendritic spines emerge and existing spines expand in size during learning and memory,” explained Halpain. “Therefore, the overall numbers and size of dendritic spines can profoundly impact the strength of neural networks. Since neural network activity underlies all brain function, changes in dendritic spine number and shape can influence cognition and behavior.”

Using neurons in culture, rather than intact animal brains, allowed the biologists to take images of the synapses at high spatial resolution using techniques called fluorescence light microscopy and confocal imaging. They also used time-lapse microscopy to observe structural changes in individual dendritic spines during exposure to isoflurane. Karl Herold, a research associate in the Hemmings laboratory and a co-author of the study, performed some of the image analysis.

“Imaging of human brain synapses at this level of detail is impossible with today’s technology and it remains very challenging even in laboratory rodents,” said Halpain. “It was important that we performed our study using rodent neurons in a culture dish, so that we could really drill down into the subcellular and molecular details of how anesthetics work.”

The researchers wondered whether brief exposure to isoflurane would alter the numbers and size of dendritic spines, so they applied the anesthetic to the cultured rat cells at concentrations and durations (up to 60 minutes) that are frequently used during surgery.

“We observed detectable decreases in dendritic spine numbers and shape within as little as 10 minutes,” said Halpain. “However this spine loss and shrinkage was reversible after the anesthetic was washed out of the culture.”

“Our study was reassuring in the sense that the effects are not irreversible and this fits in with known clinical effects,” said Hemmings. “For the most part, we find that the effects are reversible.”

“We clearly see an effect—a very marked effect on the dendritic spines—from use of this drug that was reversible, suggesting that it is not a toxic effect, but something more relevant to the pharmacological actions of the drug,” he added. “Connecting what we found to the cognitive effects of isoflurane will require much more detailed analysis.”

The team plans to follow up its study with future experiments to probe the molecular mechanisms and long-lasting consequences of isoflurane’s effects on neuron synapses and examine other commonly-used anesthetics for surgery.

(Image caption: Granule cells connect with other cells via long projections (dendrites). The actual junctions (synapses) are located on thorn-like protuberances called “spines”. Spines are shown in green in the computer reconstruction. Credit: DZNE/Michaela Müller)

A protein couple controls flow of information into the brain’s memory center

Neuroscientists in Bonn and Heidelberg have succeeded in providing new insights into how the brain works. Researchers at the DZNE and the German Cancer Research Center (DKFZ) analyzed tissue samples from mice to identify how two specific proteins, ‘CKAMP44’ and ‘TARP Gamma-8’, act upon the brain’s memory center. These molecules, which have similar counterparts in humans, affect the connections between nerve cells and influence the transmission of nerve signals into the hippocampus, an area of the brain that plays a significant role in learning processes and the creation of memories. The results of the study have been published in the journal Neuron.

Brain function depends on the active communication between nerve cells, known as neurons. For this purpose, neurons are woven together into a dense network where they constantly relay signals to one another. However, neurons do not form direct contacts with each other. Instead they are separated by an extremely narrow gap, known as the synapse. This gap is bridged by ‘neurotransmitters’, which carry nerve signals from one cell to the next.

Docking stations

How the brain stabilizes its connections in order to learn better

Throughout our lives, our brains adapt to what we learn and memorise. The brain is indeed made up of complex networks of neurons and synapses that are constantly re-configured. However, in order for learning to leave a trace, connections must be stabilized. A team at the University of Geneva (UNIGE) discovered a new cellular mechanism involved in the long-term stabilization of neuron connections, in which non-neuronal cells, called astrocytes, play a role unidentified until now. These results, published in Current Biology, will lead to a better understanding of neurodegenerative and neurodevelopmental diseases.

The central nervous system excitatory synapses – points of contact between neurons that allow them to transmit signals – are highly dynamic structures, which are continuously forming and dissolving. They are surrounded by non-neuronal cells, or glial cells, which include the distinctively star-shaped astrocytes. These cells form complex structures around synapses, and play a role in the transmission of cerebral information which was widely unknown before.

Plasticity and Stability

By increasing neuronal activity through whiskers stimulation of adult mice, the scientists were able to observe, in both the somatosensory cortex and the hippocampus, that this increased neuronal activity provokes an increase in astrocytes movements around synapses. The synapses, surrounded by astrocytes, re-organise their architecture, which protects them and increases their longevity. The team of researchers led by Dominique Muller, Professor in the Department of Fundamental Neuroscience of the Faculty of Medicine at UNIGE, developed new techniques that allowed them to specifically “control” the different synaptic structures, and to show that the phenomenon took place exclusively in the connections between neurons involved in learning. “In summary, the more the astrocytes surround the synapses, the longer the synapses last, thus allowing learning to leave a mark on memory,” explained Yann Bernardinelli, the lead author on this study.

This study identifies a new, two-way interaction between neurons and astrocytes, in which the learning process regulates the structural plasticity of astrocytes, who in turn determine the fate of the synapses. This mechanism indicates that astrocytes apparently play an important role in the processes of learning and memory, which present abnormally in various neurodegenerative and neurodevelopmental diseases, among which Alzheimer’s, autism, or Fragile X syndrome.

This discovery highlights the until now underestimated importance of cells which, despite being non-neuronal, participate in a crucial way in the cerebral mechanisms that allow us to learn and retain memories of what we have learned.