The ability to learn associations between events is critical for survival, but it has not been clear how different pieces of information stored in memory may be linked together by populations of neurons. In a study published April 2nd in Cell Reports, synchronous activation of distinct neuronal ensembles caused mice to artificially associate the memory of a foot shock with the unrelated memory of exploring a safe environment, triggering an increase in fear-related behavior when the mice were re-exposed to the non-threatening environment. The findings suggest that co-activated cell ensembles become wired together to link two distinct memories that were previously stored independently in the brain.
“Memory is the basis of all higher brain functions, including consciousness, and it also plays an important role in psychiatric diseases such as post-traumatic stress disorder,” says senior study author Kaoru Inokuchi of the University of Toyama. “By showing how the brain associates different types of information to generate a qualitatively new memory that leads to enduring changes in behavior, our findings could have important implications for the treatment of these debilitating conditions.”
Recent studies have shown that subpopulations of neurons activated during learning are reactivated during subsequent memory retrieval, and reactivation of a cell ensemble triggers the retrieval of the corresponding memory. Moreover, artificial reactivation of a specific neuronal ensemble corresponding to a pre-stored memory can modify the acquisition of a new memory, thereby generating false or synthetic memories. However, these studies employed a combination of sensory input and artificial stimulation of cell ensembles. Until now, researchers had not linked two distinct memories using completely artificial means.
With that goal in mind, Inokuchi and Noriaki Ohkawa of the University of Toyama used a fear-learning paradigm in mice followed by a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neuronal excitability, and then delivering blue light through an optic fiber to activate those cells. In the behavioral paradigm, one group of mice spent six minutes in a cylindrical enclosure while another group explored a cube-shaped enclosure, and 30 minutes later, both groups of mice were placed in the cube-shaped enclosure, where a foot shock was immediately delivered. Two days later, mice that were re-exposed to the cube-shaped enclosure spent more time frozen in fear than mice that were placed back in the cylindrical enclosure.
The researchers then used optogenetics to reactivate the unrelated memories of the safe cylinder-shaped environment and the foot shock. Stimulation of neuronal populations in memory-related brain regions called the hippocampus and amygdala, which were activated during the learning phase, caused mice to spend more time frozen in fear when they were later placed back in the cylindrical enclosure, as compared with stimulation of neurons in either the hippocampus or amygdala, or no stimulation at all.
The findings show that synchronous activation of distinct cell ensembles can generate artificial links between unrelated pieces of information stored in memory, resulting in long-lasting changes in behavior. “By modifying this technique, we will next attempt to artificially dissociate memories that are physiologically connected,” Inokuchi says. “This may contribute to the development of new treatments for psychiatric disorders such as post-traumatic stress disorder, whose main symptoms arise from unnecessary associations between unrelated memories.”
More information: Cell Reports, Ohkawa et al.: “Artificial Association of Pre-Stored Information to Generate a Qualitatively New Memory” www.cell.com/cell-reports/abst… 2211-1247(15)00270-3
The finding could mean recollections are more enduring than expected and disrupt plans for PTSD treatments.
As intangible as they may seem, memories have a firm biological basis. According to textbook neuroscience, they form when neighboring brain cells send chemical communications across the synapses, or junctions, that connect them. Each time a memory is recalled, the connection is reactivated and strengthened. The idea that synapses store memories has dominated neuroscience for more than a century, but a new study by scientists at the University of California, Los Angeles, may fundamentally upend it: instead memories may reside inside brain cells. If supported, the work could have major implications for the treatment of post-traumatic stress disorder (PTSD), a condition marked by painfully vivid and intrusive memories.
More than a decade ago scientists began investigating the drug propranolol for the treatment of PTSD. Propranolol was thought to prevent memories from forming by blocking production of proteins required for long-term storage. Unfortunately, the research quickly hit a snag. Unless administered immediately after the traumatic event, the treatment was ineffective. Lately researchers have been crafting a work-around: evidence suggests that when someone recalls a memory, the reactivated connection is not only strengthened but becomes temporarily susceptible to change, a process called memory reconsolidation. Administering propranolol (and perhaps also therapy, electrical stimulation and certain other drugs) during this window can enable scientists to block reconsolidation, wiping out the synapse on the spot.
The possibility of purging recollections caught the eye of David Glanzman, a neurobiologist at U.C.L.A., who set out to study the process in Aplysia, a sluglike mollusk commonly used in neuroscience research. Glanzman and his team zapped Aplysia with mild electric shocks, creating a memory of the event expressed as new synapses in the brain. The scientists then transferred neurons from the mollusk into a petri dish and chemically triggered the memory of the shocks in them, quickly followed by a dose of propranolol.
Initially the drug appeared to confirm earlier research by wiping out the synaptic connection. But when cells were exposed to a reminder of the shocks, the memory came back at full strength within 48 hours. “It was totally reinstated,” Glanzman says. “That implies to me that the memory wasn’t stored in the synapse.” The results were recently published in the online open-access journal eLife.
If memory is not located in the synapse, then where is it? When the neuroscientists took a closer look at the brain cells, they found that even when the synapse was erased, molecular and chemical changes persisted after the initial firing within the cell itself. The engram, or memory trace, could be preserved by these permanent changes. Alternatively, it could be encoded in modifications to the cell’s DNA that alter how particular genes are expressed. Glanzman and others favor this reasoning.
Eric R. Kandel, a neuroscientist at Columbia University and recipient of the 2000 Nobel Prize in Physiology or Medicine for his work on memory, cautions that the study’s results were observed in the first 48 hours after treatment, a time when consolidation is still sensitive.
Though preliminary, the results suggest that for people with PTSD, pill popping will most likely not eliminate painful memories. “If you had asked me two years ago if you could treat PTSD with medication blockade, I would have said yes, but now I don’t think so,” Glanzman says. On the bright side, he adds, the idea that memories persist deep within brain cells offers new hope for another disorder tied to memory: Alzheimer’s.
At some point in your life, you’ve probably been labeled a “right-brain thinker” (you’re so creative!) or a “left-brain thinker” (you’re so logical). Maybe this has shaped the way you see yourself or view the world.
“This is an idea that makes no physiological sense,” she says.
Blakemore believes that the concept of “logical, analytical, and accurate” thinkers favoring their left hemisphere and “creative, intuitive, and emotional” thinkers favoring their right hemisphere is the misinterpretation of valuable science. She thinks it entered pop culture because it makes for snappy self-help books. And of course people love categorizing themselves.
In the ’60s, ’70s, and ’80s, the renowned cognitive neuroscientist Michael Gazzaniga led breakthrough studies on how the brain works. He studied patients who — and here’s the key — lacked a corpus callosum, the tract that connect the brain’s hemispheres. During this time doctors had experimented on patients suffering from constant seizures due to intractable epilepsy by disconnecting the hemispheres.
Gazzaniga could thus determine the origins in the brain of certain cognitive and motor functions by monitoring the brains of these patients.
He found, for example, that a part of the left brain he dubbed “The Interpreter” handled the process of explaining actions that may have begun in the right brain.
He discovered “that each hemisphere played a role in different tasks and different cognitive functions, and that normally one hemisphere dominated over the other,” Blakemore explains.
This was breakthrough research on how parts of the brain worked. But in a normal human being, the corpus callosum is constantly transmitting information between both halves. It’s physically impossible to favor one side.
Blakemore thinks that this misinterpretation of the research is actually harmful, because the dichotomous labels convince people that their way of thinking is genetically fixed on a large scale.
“I mean, there are huge individual differences in cognitive strengths,” Blakemore says. “Some people are more creative; others are more analytical than others. But the idea that this has something to do with being left-brained or right-brained is completely untrue and needs to be retired.”
You can listen to Blakemore and many other experts taking down their least favorite ideas in the Freakonomics Radio episode “This Idea Must Die,” hosted by “Freakonomics” co-author Stephen J. Dubner.
»Anyone who knows me also knows that I have a huge sweet tooth. I always have. My friend and fellow graduate student Andrew is equally afflicted, and living in Hershey, Pennsylvania – the “Chocolate Capital of the World” – doesn’t help either of us.
But Andrew is braver than I am. Last year, he gave up sweets for Lent. I can’t say that I’m following in his footsteps this year, but if you are abstaining from sweets for Lent this year, here’s what you can expect over the next 40 days.
Sugar: natural reward, unnatural fix
In neuroscience, food is something we call a “natural reward.” In order for us to survive as a species, things like eating, having sex and nurturing others must be pleasurable to the brain so that these behaviours are reinforced and repeated.
Evolution has resulted in the mesolimbic pathway, a brain system that deciphers these natural rewards for us. When we do something pleasurable, a bundle of neurons called the ventral tegmental area uses the neurotransmitter dopamine to signal to a part of the brain called the nucleus accumbens. The connection between the nucleus accumbens and our prefrontal cortex dictates our motor movement, such as deciding whether or not to taking another bite of that delicious chocolate cake. The prefrontal cortex also activates hormones that tell our body: “Hey, this cake is really good. And I’m going to remember that for the future.”
Not all foods are equally rewarding, of course. Most of us prefer sweets over sour and bitter foods because, evolutionarily, our mesolimbic pathway reinforces that sweet things provide a healthy source of carbohydrates for our bodies. When our ancestors went scavenging for berries, for example, sour meant “not yet ripe,” while bitter meant “alert – poison!”
Fruit is one thing, but modern diets have taken on a life of their own. A decade ago, it was estimated that the average American consumed 22 teaspoons of added sugar per day, amounting to an extra 350 calories; it may well have risen since then. A few months ago, one expert suggested that the average Briton consumes 238 teaspoons of sugar each week.
Today, with convenience more important than ever in our food selections, it’s almost impossible to come across processed and prepared foods that don’t have added sugars for flavour, preservation, or both.
These added sugars are sneaky – and unbeknown to many of us, we’ve become hooked. In ways that drugs of abuse – such as nicotine, cocaine and heroin – hijack the brain’s reward pathway and make users dependent, increasing neuro-chemical and behavioural evidence suggests that sugar is addictive in the same way, too.
Sugar addiction is real
“The first few days are a little rough,” Andrew told me about his sugar-free adventure last year. “It almost feels like you’re detoxing from drugs. I found myself eating a lot of carbs to compensate for the lack of sugar.”
There are four major components of addiction: bingeing, withdrawal, craving, and cross-sensitisation (the notion that one addictive substance predisposes someone to becoming addicted to another). All of these components have been observed in animal models of addiction – for sugar, as well as drugs of abuse.
A typical experiment goes like this: rats are deprived of food for 12 hours each day, then given 12 hours of access to a sugary solution and regular chow. After a month of following this daily pattern, rats display behaviours similar to those on drugs of abuse. They’ll binge on the sugar solution in a short period of time, much more than their regular food. They also show signs of anxiety and depression during the food deprivation period. Many sugar-treated rats who are later exposed to drugs, such as cocaine and opiates, demonstrate dependent behaviours towards the drugs compared to rats who did not consume sugar beforehand.
Like drugs, sugar spikes dopamine release in the nucleus accumbens. Over the long term, regular sugar consumption actually changes the gene expression and availability of dopamine receptors in both the midbrain and frontal cortex. Specifically, sugar increases the concentration of a type of excitatory receptor called D1, but decreases another receptor type called D2, which is inhibitory. Regular sugar consumption also inhibits the action of the dopamine transporter, a protein which pumps dopamine out of the synapse and back into the neuron after firing.
In short, this means that repeated access to sugar over time leads to prolonged dopamine signalling, greater excitation of the brain’s reward pathways and a need for even more sugar to activate all of the midbrain dopamine receptors like before. The brain becomes tolerant to sugar – and more is needed to attain the same “sugar high.”
Sugar withdrawal is also real
Although these studies were conducted in rodents, it’s not far-fetched to say that the same primitive processes are occurring in the human brain, too. “The cravings never stopped, [but that was] probably psychological,” Andrew told me. “But it got easier after the first week or so.”
In a 2002 study by Carlo Colantuoni and colleagues of Princeton University, rats who had undergone a typical sugar dependence protocol then underwent “sugar withdrawal.” This was facilitated by either food deprivation or treatment with naloxone, a drug used for treating opiate addiction which binds to receptors in the brain’s reward system. Both withdrawal methods led to physical problems, including teeth chattering, paw tremors, and head shaking. Naloxone treatment also appeared to make the rats more anxious, as they spent less time on an elevated apparatus that lacked walls on either side.
Similar withdrawal experiments by others also report behaviour similar to depression in tasks such as the forced swim test. Rats in sugar withdrawal are more likely to show passive behaviours (like floating) than active behaviours (like trying to escape) when placed in water, suggesting feelings of helplessness.
A new study published by Victor Mangabeira and colleagues in this month’s Physiology & Behavior reports that sugar withdrawal is also linked to impulsive behaviour. Initially, rats were trained to receive water by pushing a lever. After training, the animals returned to their home cages and had access to a sugar solution and water, or just water alone. After 30 days, when rats were again given the opportunity to press a lever for water, those who had become dependent on sugar pressed the lever significantly more times than control animals, suggesting impulsive behaviour.
These are extreme experiments, of course. We humans aren’t depriving ourselves of food for 12 hours and then allowing ourselves to binge on soda and doughnuts at the end of the day. But these rodent studies certainly give us insight into the neuro-chemical underpinnings of sugar dependence, withdrawal, and behaviour.
Through decades of diet programmes and best-selling books, we’ve toyed with the notion of “sugar addiction” for a long time. There are accounts of those in “sugar withdrawal” describing food cravings, which can trigger relapse and impulsive eating. There are also countless articles and books about the boundless energy and new-found happiness in those who have sworn off sugar for good. But despite the ubiquity of sugar in our diets, the notion of sugar addiction is still a rather taboo topic.
Are you still motivated to give up sugar for Lent? You might wonder how long it will take until you’re free of cravings and side-effects, but there’s no answer – everyone is different and no human studies have been done on this. But after 40 days, it’s clear that Andrew had overcome the worst, likely even reversing some of his altered dopamine signalling. “I remember eating my first sweet and thinking it was too sweet,” he said. “I had to rebuild my tolerance.”
And as regulars of a local bakery in Hershey – I can assure you, readers, that he has done just that.«
Sleep is a critical period for memory consolidation, and most people don’t get enough. Research has shown that even brief periods of sleep deprivation can lead to deficits in memory formation.
In a new study, published in the Journal of Neuroscience, a team led by scientists from the University of Pennsylvania found that a particular set of cells in a small region of the brain are responsible for memory problems after sleep loss. By selectively increasing levels of a signaling molecule in these cells, the researchers prevented mice from having memory deficits.
Robbert Havekes was the lead author on the study. He is a research associate in the lab of Ted Abel, the study’s senior author and Brush Family Professor of Biology in Penn’s School of Arts & Sciences. Coauthors from the Abel lab included Jennifer C. Tudor and Sarah L. Ferri. They collaborated with Arnd Baumann of Forschungszentrum Jülich, Germany, and Vibeke M. Bruinenberg and Peter Meerlo of the University of Groningen, The Netherlands.
In 2009, a group from Abel’s lab published a study in Nature that identified the cyclic AMP, or cAMP, signaling pathway as playing a role in sleep-loss-associated memory problems. Whereas depriving mice of sleep impaired their spatial memory, restoring levels of cAMP in their brain prevented this effect.
“The challenge following this important study,” Abel said, “was to determine if the impact of sleep deprivation was mediated by particular regions of the brain and particular neural circuits. We suspected that the hippocampus, the brain region that mediates spatial navigation and contextual memory, was critical.”
In the current work, they set out to answer these questions. They targeted excitatory neurons because of their importance in transmitting signals in the brain and the fact that their functioning relies on cAMP signaling. The limitation of previous studies was that they lacked a way to increase cAMP in just one area of the brain in a cell-type specific fashion. Havekes, Abel and colleagues devised a way of doing this that they term a “pharmacogenetic” approach, blending genetic modification and drug administration.
They engineered a non-pathogenic virus to harbor the gene encoding the receptor for the protein octopamine, which triggers cAMP pathway activation in fruit flies but is not naturally found in the brains of mice. The researchers injected this virus into the hippocampus of mice so that the excitatory neurons in that region alone would express the octopamine receptor.
“It sounds weird. Why would you put a receptor there that is never going to be activated?” Havekes said. “The trick is, you follow that up by giving mice the ligand of the receptor, which is octopamine, and that will activate the receptors only where they are present.”
The team confirmed that only the excitatory hippocampal neurons expressed the receptor and that they could selectively increase cAMP levels in only these cells by giving the mice a systemic injection of octopamine.
“This way, we could manipulate the cAMP pathways that we previously saw being affected by sleep deprivation but selectively in specific neural circuits in the brain,” Havekes says.
With this pharmacogenetic tool in hand, Havekes, Abel and colleagues began the sleep deprivation tests with the mice expressing the octopamine receptor in their hippocampus. First the researchers trained mice in a spatial memory task. They put them in a box that had three different objects, each in a distinct location.
Then, because previous research had shown that cAMP signaling contributes to hippocampus-dependent memory consolidation in two time windows—first directly after training and again three to four hours after training—the researchers gave mice in the experimental groups injections of octopamine in both of these windows to boost cAMP levels.
Mice receiving the cAMP boost were divided into two groups: One was left to sleep undisturbed, while the other was sleep-deprived for five hours by gently tapping their cage or rearranging their bedding.
One full day after the initial training, all of the mice were tested again. This time, there was a twist: one of the objects originally in the box had been moved to a new location.
“If the mice had learned and remembered the location of the objects during their training, then they would realize, okay, this is the object that has moved, and they’ll spend more time exploring that particular object,” Havekes explained. “If they didn’t remember well, they would explore all the objects in a random fashion.”
The researchers found that the sleep-deprived mice that received the octopamine injections spent more time exploring the object that had moved, just as mice that had not been sleep deprived did. On the other hand, sleep-deprived mice that didn’t express the receptor explored all the objects at random, a sign that they had failed to remember the locations of the objects from their initial training as a result of the brief period of sleep deprivation.
“What we’ve shown is this memory loss due to sleep deprivation is really dependent on misregulation of cAMP signaling in the excitatory neurons of the hippocampus,” Havekes said.
As a next step, the group would like to explore what cAMP is doing to help consolidate memory. They would also like to investigate how other cell types in the brain, such as astrocytes, might be affected. And finally, while this study focused on the impact of a brief period of sleep deprivation, Havekes is curious to know how not getting enough sleep on a daily basis, as is more similar to human experiences, might be affecting memory.
“Thinking about people who do shift work or doctors who work long hours, if we can tackle the cognitive problems that result from sleep loss, that would be a great thing,” Havekes said.
“At least in the mouse using these sophisticated tools, we’re able to reverse the negative impact of sleep deprivation on cognition,” Abel said.
Grad student Chi Lu and colleagues demonstrate a highly flexible polymer probe for triggering spinal-cord neurons with light and simultaneously recording their activity.
MIT researchers have demonstrated a highly flexible neural probe made entirely of polymers that can both optically stimulate and record neural activity in a mouse spinal cord — a step toward developing prosthetic devices that can restore functionality to damaged nerves.
“Our goal was to create a tool that would enable neuroscientists and physicians to investigate spinal-cord function on both cellular and systems levels with minimal impact on the tissue integrity,” notes Polina Anikeeva, the AMAX Assistant Professor in Materials Science and Engineering and a senior author of the paper published Nov. 7 in Advanced Functional Materials.
Department of Materials Science and Engineering graduate student Chi (Alice) Lu, who designed and implanted the probe, is the lead author of the study. Co-authors include Ulrich Froriep of the Simons Center for the Social Brain; Ryan Koppes of the Research Laboratory of Electronics; Andres Canales and Jennifer Selvidge of the Department of Materials Science and Engineering; and Vittorio Caggiano and Emilio Bizzi of the McGovern Institute for Brain Research. Professor Yoel Fink provided access to the fiber-drawing tower.
Although optogenetics, a method that makes mammalian nerve cells sensitive to light via genetic modification, has been applied extensively in investigation of brain function over the past decade, spinal-cord research has lagged. Earlier this year Caggiano and Bizzi have demonstrated inhibition of motor functions using optogenetics, and now the collaboration between the two groups yielded a device suitable for spinal optical excitation of muscle activity, while giving the researchers an electrical readout.
“Working in a spinal cord is significantly more difficult than in the brain because it experiences more movements. The radius of the mouse spinal cord is about 1 millimeter, and it is very soft, so it took some time to figure out how to design a device that would perform the stimulation and recording without damaging that tissue,” Lu explains.
The fiber was drawn from a template nearly 1.5 inches thick to its final diameter comparable to that of a human hair. It is flexible enough to be tied in a knot. The probe consists of a transparent polycarbonate optical core; parallel conductive polyethylene electrodes for recording neuronal electrical activity; and cyclic olefin copolymer acting both as electrical insulation and optical cladding. The flexible probe maintains its optical and electrical functions when bent by up to 270 degrees at very small radii of curvature (e.g. 500 µm), albeit with somewhat diminished light-carrying capacity at those conditions. The device still performed well after repeated bending and straightening, holding up under stresses expected from normal body movements, the report shows. MIT has filed a patent on the device platform.
The researchers conducted experiments with their neural probe in genetically-altered mice that express the light-sensitive protein channelrhodopsin 2 (ChR2) labeled with yellow fluorescent protein. The ChR2 makes neurons in the mice respond to blue light. These mice, developed by Professor Guoping Feng and colleagues at the McGovern Institute for Brain Research, provide a convenient model system for optoelectronic neural prosthetics. “When pulses of blue light are delivered to the spinal cord, we can directly observe neuronal response by getting an electrical recording,” explains Lu, who entered the third year of her doctoral program this fall.
“Laser pulses … delivered through the [polycarbonate] core of the fiber probe robustly evoked neural activity in the spinal cord, as recorded with the … electrodes integrated within the same device,” the researchers report.
The fiber was inserted into the proximal lumbar section of the spinal cord in mice, and light delivered through it triggered activity in one of the calf muscles, the gastrocnemius muscle. The results in the optically-sensitive mice were validated by comparison with results in wild type mice, which showed no response to the optical trigger. A toe pinch showed the device could still record mechanically stimulated neuronal activity in the wild-type mice. The researchers monitored muscle activity through electromyographical (EMG) recording, while the conductive polyethylene electrodes in the new device recorded neuronal activity in the spinal cord.
The MIT researchers’ combination in a single system of both recording activity from neurons and stimulating neurons with light is new, says Ravi V. Bellamkonda, the Wallace H. Coulter Professor and Department Chair of Biomedical Engineering at Georgia Institute of Technology and the Emory School of Medicine. “In principle, one would like to use ‘closed-loop’ systems, i.e., you detect a neurological event — like the brain wanting to move a limb — and then stimulate to affect that function when the natural link between them is severed due to an injury like spinal cord damage,” he explains.
“This is excellent engineering combining electrical and optical engineering for an important biological application — modulation of neural function in a closed-loop way. I am eager to see this technology being used in a biologically significant ways in the future,” Bellamkonda says.
The work was funded in part by grants from the National Science Foundation through the Center for Sensorimotor Neural Engineering and Center for Materials Science and Engineering; the McGovern Institute for Brain Research Neurotechnology Program; and the Simons Foundation.
Source: MIT press release
Image Source: The image is credited to the Chi (Alice) Lu and Polina Anikeeva and is adapted from the MIT press release
Original Research: Abstract for “Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo” by Chi Lu, Ulrich P. Froriep, Ryan A. Koppes, Andres Canales, Vittorio Caggiano, Jennifer Selvidge, Emilio Bizzi and Polina Anikeeva in Advanced Functional Materials. Published online August 26 2014 doi:10.1002/adfm.201401266
Animal study highlights potential new target for treating anxiety disorders
Increasing acidity in the brain’s emotional control center reduces anxiety, according to an animal study published February 26 in The Journal of Neuroscience. The findings suggest a new mechanism for the body’s control of fear and anxiety, and point to a new target for the treatment of anxiety disorders.
Anxiety disorders, which are characterized by an inability to control feelings of fear and uncertainty, are the most prevalent group of psychiatric diseases. At the cellular level, these disorders are associated with heightened activity in the basolateral amygdala (BLA), which is known to play a central role in emotional behavior.
Many cells in the BLA possess acid-sensing ion channels called ASIC1a, which respond to pH changes in the environment outside of the cell. Maria Braga, DDS, PhD, and colleagues at the Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, found that activating ASIC1a decreased the activity of nearby cells and reduced anxiety-like behavior in animals. These findings add to previous evidence implicating the role of ASIC1a in anxiety.
“These findings suggest that activating these channels, specifically in fear-related areas such as the amygdala, may be a key to regulating anxiety,” explained Anantha Shekhar, MD, PhD, who studies panic disorders at Indiana University and was not involved in this study. “Developing specific drugs that can stimulate these channels could provide a new way to treat anxiety and fear disorders such a post-traumatic stress and panic disorders.”
To determine the effect ASIC1a activation has on neighboring cells, Braga’s group bathed BLA cells in an acidic solution in the laboratory and measured the signals sent to nearby cells. Lowering the pH of the solution decreased the activity of cells in the BLA.
Activating ASIC1a also affected animal behavior. When the researchers administered a drug that blocks ASIC1a directly into the BLA of rats, the rats displayed more anxiety-like behavior than animals that did not receive the drug. In contrast, when rats received a drug designed to increase the activity of ASIC1a channels in the BLA, the animals displayed less anxiety-like behavior.
“Our study emphasizes the importance of identifying and elucidating mechanisms involved in the regulation of brain function for the development of more efficacious therapies for treating psychiatric and neurological illnesses,” Braga said. While the findings suggest that drugs targeting ASICs may one day lead to novel therapies for anxiety disorders, Braga noted that “more research is needed to understand the roles that ASIC1a channels play in the brain.”
Link to the article: