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.”
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Swedish researchers at Uppsala University have, together with Brazilian collaborators, discovered a new group of nerve cells that regulate processes of learning and memory. These cells act as gatekeepers and carry a receptor for nicotine, which can help explain our ability to remember and sort information.
The discovery of the gatekeeper cells, which are part of a memory network together with several other nerve cells in the hippocampus, reveal new fundamental knowledge about learning and memory. The study is published today in Nature Neuroscience.
The hippocampus is an area of the brain that is important for consolidation of information into memories and helps us to learn new things. The newly discovered gatekeeper nerve cells, also called OLM-alpha2 cells, provide an explanation to how the flow of information is controlled in the hippocampus. Read more…
Simply activating a tiny number of neurons can conjure an entire memory.
Our fond or fearful memories — that first kiss or a bump in the night — leave memory traces that we may conjure up in the remembrance of things past, complete with time, place and all the sensations of the experience. Neuroscientists call these traces memory engrams.
But are engrams conceptual, or are they a physical network of neurons in the brain? In a new MIT study, researchers used optogenetics to show that memories really do reside in very specific brain cells, and that simply activating a tiny fraction of brain cells can recall an entire memory — explaining, for example, how Marcel Proust could recapitulate his childhood from the aroma of a once-beloved madeleine cookie.
“We demonstrate that behavior based on high-level cognition, such as the expression of a specific memory, can be generated in a mammal by highly specific physical activation of a specific small subpopulation of brain cells, in this case by light,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study reported online today in the journal Nature. “This is the rigorously designed 21st-century test of Canadian neurosurgeon Wilder Penfield’s early-1900s accidental observation suggesting that mind is based on matter.” Read more…
Why the Thrill is Gone: Scientists Identify Potential Target for Treating Major Symptom of Depression
Stanford University School of Medicine scientists have laid bare a novel molecular mechanism responsible for the most important symptom of major depression: anhedonia, the loss of the ability to experience pleasure. While their study was conducted in mice, the brain circuit involved in this newly elucidated pathway is largely identical between rodents and humans, upping the odds that the findings point toward new therapies for depression and other disorders.
Additionally, opinion leaders hailed the study’s inventive methodology, saying it may offer a much sounder approach to testing new antidepressants than the methods now routinely used by drug developers.
While as many as one in six Americans is likely to suffer a major depression in their lifetimes, current medications either are inadequate or eventually stop working in as many as 50 percent of those for whom they’re prescribed.
“This may be because all current medications for depression work via the same mechanisms,” said Robert Malenka, MD, PhD, the Nancy Friend Pritzker Professor in Psychiatry and Behavioral Sciences. “They increase levels of one or another of two small molecules that some nerve cells in the brain use to signal one another. To get better treatments, there’s a great need to understand in greater detail the brain biology that underlies depression’s symptoms.” The study’s first author is Byung Kook Lim, PhD, a postdoctoral scholar in Malenka’s laboratory.
Malenka is senior author of the new study, published July 12 in Nature, which reveals a novel drug target by showing how a hormone known to affect appetite turns off the brain’s ability to experience pleasure when an animal is stressed. This hormone, melanocortin, signals to an ancient and almost universal apparatus deep in the brain called the reward circuit, which has evolved to guide animals toward resources, behaviors and environments — such as food, sex and warmth — that enhance their prospects for survival.
Scientists found that both chronic stress and the direct administration of melanocortin diminished the signaling strength of some synapses in the nucleus accumbens that contain receptors for melanocortin. The nucleus accumbens is labeled in this drawing of a human brain cross section. (up)
“This is the first study to suggest that we should look at the role of melanocortin in depression-related syndromes,” said Eric Nestler, MD, PhD, professor and chair of neuroscience and director of the Friedman Brain Institute at Mount Sinai School of Medicine in New York. Nestler was not involved in the study but is familiar with its contents. Read more…
Researchers have figured out the speed that neural networks in the cerebral cortex can delete sensory information is a bit of information per active neuron per second. The activity patterns of the neural network models are deleted nearly as soon as they are passed on from sensory neurons.
The scientists used neural network models based on real neuronal properties for the first time for these calculations. Neuronal spike properties were figured into the models which also helped show that the cerebral cortex processes were extremely chaotic.
Neural networks and this type of research in general are all helping researchers better understand learning and memory processes. With better knowledge about learning and memory, researchers can work toward treatments for Alzheimer’s disease, dementia, learning disabilities, PTSD related memory loss and many other problems.
More details are provided in the release below. Read more…
Taking a trip down memory lane while you are driving could land you in a roadside ditch, new research indicates.
Vanderbilt University psychologists have found that our visual perception can be contaminated by memories of what we have recently seen, impairing our ability to properly understand and act on what we are currently seeing.
“This study shows that holding the memory of a visual event in our mind for a short period of time can ‘contaminate’ visual perception during the time that we’re remembering,” Randolph Blake, study co-author and Centennial Professor of Psychology, said.
“Our study represents the first conclusive evidence for such contamination, and the results strongly suggest that remembering and perceiving engage at least some of the same brain areas.” Read more…
A new method facilitates the mapping of connections between neurons.
The human brain accomplishes its remarkable feats through the interplay of an unimaginable number of neurons that are interconnected in complex networks. A team of scientists from the Max Planck Institute for Dynamics and Self-Organization, the University of Göttingen and the Bernstein Center for Computational Neuroscience Göttingen has now developed a method for decoding neural circuit diagrams. Using measurements of total neuronal activity, they can determine the probability that two neurons are connected with each other.
The human brain consists of around 80 billion neurons, none of which lives or functions in isolation. The neurons form a tight-knit network that they use to exchange signals with each other. The arrangement of the connections between the neurons is far from arbitrary, and understanding which neurons connect with each other promises to provide valuable information about how the brain works. At this point, identifying the connection network directly from the tissue structure is practically impossible, even in cell cultures with only a few thousand neurons. In contrast, there are currently well-developed methods for recording dynamic neuronal activity patterns. Such patterns indicate which neuron transmitted a signal at what time, making them a kind of neuronal conversation log. The Göttingen-based team headed by Theo Geisel, Director at the Max Planck Institute for Dynamics and Self-Organization, has now made use of these activity patterns. Read more…