Posts tagged memory
Posts tagged memory
Researchers at The Scripps Research Institute (TSRI) and Vanderbilt University have created the most detailed 3-D picture yet of a membrane protein that is linked to learning, memory, anxiety, pain and brain disorders such as schizophrenia, Parkinson’s, Alzheimer’s and autism.
"This receptor family is an exciting new target for future medicines for treatment of brain disorders," said P. Jeffrey Conn, PhD, Lee E. Limbird Professor of Pharmacology and director of the Vanderbilt Center for Neuroscience Drug Discovery, who was a senior author of the study with Raymond Stevens, PhD, a professor in the Department of Integrative Structural and Computational Biology at TSRI. "This new understanding of how drug-like molecules engage the receptor at an atomic level promises to have a major impact on new drug discovery efforts."
The research—which focuses on the mGlu1 receptor—was reported in the March 6, 2014 issue of the journal Science.
A Family of Drug Targets
The mGlu1 receptor, which helps regulate the neurotransmitter glutamate, belongs to a superfamily of molecules known as G protein-coupled receptors (GPCRs).
GPCRs sit in the cell membrane and sense various molecules outside the cell, including odors, hormones, neurotransmitters and light. After binding these molecules, GPCRs trigger a specific response inside the cell. More than one-third of therapeutic drugs target GPCRs—including allergy and heart medications, drugs that target the central nervous system and anti-depressants.
The Stevens lab’s work has revolved around determining the structure and function of GPCRs. GPCRs are not well understood and many fundamental breakthroughs are now occurring due to the understanding of GPCRs as complex machines, carefully regulated by cholesterol and sodium.
When the Stevens group decided to pursue the structure of mGlu1 and other key members of the mGlu family, it was natural the scientists reached out to the researchers at Vanderbilt. “They are the best in the world at understanding mGlu receptors,” said Stevens. “By collaborating with experts in specific receptor subfamilies, we can reach our goal of understanding the human GPCR superfamily and how GPCRs control human cell signaling.”
Colleen Niswender, PhD, director of Molecular Pharmacology and research associate professor of Pharmacology at the Vanderbilt Center for Neuroscience Drug Discovery, also thought the collaboration made sense. “This work leveraged the unique strengths of the Vanderbilt and Scripps teams in applying structural biology, molecular modeling, allosteric modulator pharmacology and structure-activity relationships to validate the receptor structure,” she said.
The Challenge of the Unknown
mGlu1 was a particularly challenging research topic.
In general, GPCRs are exceedingly flimsy, fragile proteins when not anchored within their native cell membranes. Coaxing them to line up to form crystals, so that their structures can be determined through X-ray crystallography, has been a formidable challenge. And the mGlu1 receptor is particularly tricky as, in addition to the domain spanning the membrane, it has a large domain extending into the extracellular space. Moreover, two copies of this multidomain receptor associating in a dimer are needed to transmit glutamate’s signal across the membrane.
The task was made more difficult because there was no template for mGlu1 from closely related GPCR proteins to guide the researchers.
“mGlu1 belongs to class C GPCRs, of which no structure has been solved before,” said TSRI graduate student Chong Wang, a first author of the new study with TSRI graduate student Huixian Wu. “This made the project much harder. We could not use other GPCRs as a template to design constructs for expression and stabilization or to help interpret diffraction data. The structure was so different that old school methods in novel protein structure determination had to be used.”
The team decided to try to determine the structure of mGlu1 bound to novel “allosteric modulators” of mGlu1 contributed by the Vanderbilt group. Allosteric modulators bind to a site far away from the binding site of the natural activator (in this case, presumably the glutamate molecule), but change the shape of the molecule enough to affect receptor function. In the case of allosteric drug candidates, the hope is that the compounds affect the receptor function in a desirable, therapeutic way.
"Allosteric modulators are promising drug candidates as they can ‘fine-tune’ GPCR function,” said Karen Gregory, a former postdoctoral fellow at Vanderbilt University, now at Monash Institute of Pharmaceutical Sciences. “However, without a good idea of how drug-like compounds interact with the receptor to adjust the strength of the signal, discovery efforts are challenging."
The team proceeded to apply a combination of techniques, including X-ray crystallography, structure-activity relationships, mutagenesis and full-length dimer modeling. At the end of the study, they had achieved a high-resolution image of mGlu1 in complex with one of the drug candidates, as well as a deeper understanding of the receptor’s function and pharmacology.
The findings show that mGlu1 possesses structural features both similar to and distinct from those seen in other GPCR classes, but in ways that would have been impossible to predict in advance.
“Most surprising is that the entrance to a binding pocket in the transmembrane domain is almost completely covered by loops, restricting access for the binding of allosteric modulators,” said Vsevolod “Seva” Katritch, assistant professor of molecular biology at TSRI and a co-author of the paper. “This is very important for understanding action of the allosteric modulator drugs and may partially explain difficulties in screening for such drugs.
“The mGlu1 receptor structure now provides a solid platform for much more reliable modeling of closely related receptors,” he continued, “some of which are equally important in drug discovery.”
It may seem normal: As we age, we misplace car keys, or can’t remember a name we just learned or a meal we just ordered. But University of Florida researchers say memory trouble doesn’t have to be inevitable, and they’ve found a drug therapy that could potentially reverse this type of memory decline.
The drug can’t yet be used in humans, but the researchers are pursuing compounds that could someday help the population of aging adults who don’t have Alzheimer’s or other dementias but still have trouble remembering day-to-day items. Their findings will be published in today’s (March 5) issue of the Journal of Neuroscience.
The kind of memory responsible for holding information in the mind for short periods of time is called “working memory.” Working memory relies on a balance of chemicals in the brain. The UF study shows this chemical balance tips in older adults, and working memory declines. The reason? It could be because their brains are producing too much of a chemical that slows neural activity.
“Graduate student Cristina Banuelos’ work suggests that cells that normally provide the brake on neural activity are in overdrive in the aged prefrontal cortex,” said researcher Jennifer Bizon, Ph.D., an associate professor in the department of neuroscience and a member of UF’s Evelyn F. & William L. McKnight Brain Institute.
This chemical, an inhibitory brain neurotransmitter called GABA, is essential. Without it, brain cells can become too active, similar to what happens in the brains of people with schizophrenia and epilepsy. A normal level of GABA helps maintain the optimal levels of cell activation, said collaborator Barry Setlow, Ph.D., an associate professor in UF’s departments of psychiatry and neuroscience.
Working memory underlies many mental abilities and is sometimes referred to as the brain’s mental sketchpad, Bizon said. For example, Bizon said, you use your working memory in many everyday activities such as calculating your final bill at the end of dining at a restaurant. Most people can calculate a 15 percent tip and add it to the cost of their meal without pencil and paper. Central to this process is the ability to keep multiple pieces of information in mind for a short duration — such as remembering the cost of your dinner while calculating the amount needed for the tip.
“Almost all higher cognitive processes depend on this fundamental operation,” Bizon said.
To determine the culprit behind working memory decline, the researchers tested the memory of young and aged rats in a “Skinner box.” In the Skinner box, rats had to remember the location of a lever for short periods of up to 30 seconds. The scientists found that while both young and old rats could remember the location of the lever for brief periods of time, as those time periods lengthened, old rats had more difficulty remembering the location of the lever than young rats.
But not all older rats did poorly on the memory test, just as not all older adults have memory problems. The study shows the older brains of some people or rats with no memory problems might compensate for the overactive inhibitory system — they are able to produce fewer GABA receptors and therefore bind less of the inhibitory chemical.
Older rats with memory problems had more GABA receptors. The drug the researchers tested blocked GABA receptors, mimicking the lower number of those receptors that some older rats had naturally and restoring working memory in aged rats to the level of younger rats.
“Modern medicine has done a terrific job of keeping us alive for longer, and now we have to keep up and determine how to maximize the quality of life for seniors,” Bizon said. “A key aspect of that is going to be developing strategies and therapies that can maintain and improve cognitive health.”
Odors have a way of connecting us with moments buried deep in our past. Maybe it is a whiff of your grandmother’s perfume that transports you back decades. With that single breath, you are suddenly in her living room, listening as the adults banter about politics. The experiences that we accumulate throughout life build expectations that are associated with different scents. These expectations are known to influence how the brain uses and stores sensory information. But researchers have long wondered how the process works in reverse: how do our memories shape the way sensory information is collected?
In work published today in Nature Neuroscience, scientists from Cold Spring Harbor Laboratory (CSHL) demonstrate for the first time a way to observe this process in awake animals. The team, led by Assistant Professor Stephen Shea, was able to measure the activity of a group of inhibitory neurons that links the odor-sensing area of the brain with brain areas responsible for thought and cognition. This connection provides feedback so that memories and experiences can alter the way smells are interpreted.
The inhibitory neurons that forget the link are known as granule cells. They are found in the core of the olfactory bulb, the area of the mouse brain responsible for receiving odor information from the nose. Granule cells in the olfactory bulb receive inputs from areas deep within the brain involved in memory formation and cognition. Despite their importance, it has been almost impossible to collect information about how granule cells function. They are extremely small and, in the past, scientists have only been able to measure their activity in anesthetized animals. But the animal must be awake and conscious in order to for experiences to alter sensory interpretation. Shea worked with lead authors on the study, Brittany Cazakoff, graduate student in CSHL’s Watson School of Biological Sciences, and Billy Lau, Ph.D., a postdoctoral fellow. They engineered a system to observe granule cells for the first time in awake animals.
Granule cells relay the information they receive from neurons involved in memory and cognition back to the olfactory bulb. There, the granule cells inhibit the neurons that receive sensory inputs. In this way, “the granule cells provide a way for the brain to ‘talk’ to the sensory information as it comes in,” explains Shea. “You can think of these cells as conduits which allow experiences to shape incoming data.”
Why might an animal want to inhibit or block out specific parts of a stimulus, like an odor? Every scent is made up of hundreds of different chemicals, and “granule cells might help animals to emphasize the important components of complex mixtures,” says Shea. For example, an animal might have learned through experience to associate a particular scent, such as a predator’s urine, with danger. But each encounter with the smell is likely to be different. Maybe it is mixed with the smell of pine on one occasion and seawater on another. Granule cells provide the brain with an opportunity to filter away the less important odors and to focus sensory neurons only on the salient part of the stimulus.
Now that it is possible to measure the activity of granule cells in awake animals, Shea and his team are eager to look at how sensory information changes when the expectations and memories associated with an odor change. “The interplay between a stimulus and our expectations is truly the merger of ourselves with the world. It exciting to see just how the brain mediates that interaction,” says Shea.
Particular smells can be incredibly evocative and bring back very clear, vivid memories.
Maybe you find the smell of freshly baked apple pie is forever associated with warm memories of grandma’s kitchen. Perhaps cut grass means long school holidays and endless football kickabouts. Or maybe catching the scent of certain medicines sees you revisit a bout of childhood illness.
What’s remarkable about the power of these ‘associative memories’ – connecting sensory information and past experiences – is just how precise they are. How do we and other animals attach distinct memories to the millions of possible smells we encounter?
There’s a clear advantage in doing so: accurately discriminating smells indicating dangers while making no mistakes in following those that are advantageous. But it’s a huge information processing challenge.
Researchers at Oxford University’s Centre for Neural Circuits and Behaviour have discovered that a key to forming distinct associative memories lies in how information from the senses is encoded in the brain.
Their study in fruit flies for the first time gives experimental confirmation of a theory put forward in the 1960s which suggested sensory information is encoded ‘sparsely’ in the brain.
The idea is that we have a huge population of nerve cells in many of our higher brain centres. But only a very few neurons fire in response to any particular sensation – be it smell, sound or vision. This would allow the brain to discriminate accurately between even very similar smells and sensations.
'This “sparse” coding means that neurons that respond to one odour don't overlap much with neurons that respond to other odours, which makes it easier for the brain to tell odours apart even if they are very similar,' explains Dr Andrew Lin, the lead author of the study published in Nature Neuroscience.
While previous studies have indicated that sensory information is encoded sparsely in the brain, there’s been no evidence that this arrangement is beneficial to storing distinct memories and acting on them.
'Sparse coding has been observed in the brains of other organisms, and there are compelling theoretical arguments for its importance,' says Professor Gero Miesenböck, in whose laboratory the research was performed. 'But until now it hasn’t been possible experimentally to link sparse coding with behaviour.'
In their new work, the researchers demonstrated that if they interfered with the sparse coding in fruit flies – if they ‘de-sparsened’ odour representations in the neurons that store associative memories – the flies lost the ability to form distinct memories for similar smells.
The flies are normally able to discriminate between two very similar odours, learning to avoid one and head for the other. This is controlled by the neurons that store associative memories, called Kenyon cells. There’s a separate nerve cell that acts as a control system to dampen down the activity the Kenyon cells, preventing too many of them from firing for any particular odour.
Dr Lin and colleagues showed that if this single nerve cell is blocked, the odour coding in Kenyon cells becomes less sparse and less able to discriminate between smells. The flies end up attaching the same memory to similar, yet different, odours.
Sparse coding does turn out to be important for sensory memories and our ability to act on them. Although the research was carried out in fruit flies, the scientists say sparse coding is likely to play a similar role in human memory.
Although sparse coding in the brain would seem to require much greater numbers of nerve cells, that cost appears to be worth it in being able to form distinct associative memories and act on them – thankfully. A life of experiences and memories is so much more full as a result.
So why do neurons respond in this remarkable way? A new study by Professor Jeff Bowers and colleagues at the University of Bristol argues that highly selective neural representations are well suited to co-activating multiple things, such as words, objects and faces, at the same time in short-term memory.
The researchers trained an artificial neural network to remember words in short-term memory. Like a brain, the network was composed of a set of interconnected units that activated in response to inputs; the network ‘learnt’ by changing the strength of connections between units. The researchers then recorded the activation of the units in response to a number of different words.
When the network was trained to store one word at a time in short-term memory, it learned highly distributed codes such that each unit responded to many different words. However, when it was trained to store multiple words at the same time in short-term memory it learned highly selective (‘grandmother cell’) units – that is, after training, single units responded to one word but not any other. This is much like the neurons in the cortex that respond to one face amongst many.
Why did the network learn such highly specific representations when trained to co-activate multiple words at the same time? Professor Bowers and colleagues argue that the non-selective representations can support memory for a single word, given that a pattern of activation across many non-selective units can uniquely represent a specific word. However, when multiple patterns are mixed together, the resulting blend pattern is often ambiguous (the so-called ‘superposition catastrophe’).
This ambiguity is easily avoided, however, when the network learns to represent words in a highly selective manner, for example, if one unit codes for the word RACHEL, another for MONICA, and yet another JOEY, there is no ambiguity when the three units are co-activated.
Professor Bowers said: “Our research provides a possible explanation for the discovery that single neurons in the cortex respond to information in a highly selective manner. It’s possible that the cortex learns highly selective codes in order to support short-term memory.”
The study is published in Psychological Review.
Researchers report that one tiny variation in the sequence of a gene may cause some people to be more impaired by traumatic brain injury (TBI) than others with comparable wounds.
The study, described in the journal PLOS ONE, measured general intelligence in a group of 156 Vietnam War veterans who suffered penetrating head injuries during the war. All of the study subjects had damage to the prefrontal cortex, a brain region behind the forehead that is important to cognitive tasks such as planning, problem-solving, self-restraint and complex thought.
The researchers controlled for the size and location of subjects’ brain injuries and other factors, such as intelligence prior to injury, which might have contributed to differences in cognitive function. (Prior to combat, the veterans had completed the Armed Forces Qualifications Test, which included measures of intelligence that provided a baseline for the new analysis.)
“We administered a large, cognitive battery of tests to investigate how they performed after their injury,” said study leader Aron Barbey, a professor of speech and hearing science, of psychology and of neuroscience at the University of Illinois. “And we had a team of neurologists who helped characterize the nature and scope of the patients’ brain injuries.”
The researchers also collected blood for a genetic analysis, focusing on a gene known as BDNF (brain-derived neurotrophic factor).
The team found that a single polymorphism (a difference in one “letter” of the sequence) in the BDNF gene accounted for significant differences in intelligence among those with similar injuries and comparable intelligence before being injured.
“BDNF is a basic growth factor and it’s related to neurogenesis, the production of new neurons,” Barbey said. “What we found is that if people have a specific polymorphism in the BDNF gene, they recovered to a greater extent than those with a different variant of the gene.”
The change in the gene alters the BDNF protein: The amino acid methionine (Met) is incorporated at a specific site in the protein instead of valine (Val). Since people inherit two versions of each gene, one from each parent, they have either Val/Val, Val/Met or Met/Met variants of the gene.
“The effects of this difference were large – very large,” Barbey said. “If an individual had the Val/Val combination, then their performance on a battery of cognitive tests (conducted long after the injury occurred) was remarkably lower than that of individuals who had the Val/Met or Met/Met combination.”
On average, those with the Val/Val polymorphism scored about eight IQ points lower on tests of general intelligence than those with the Val/Met or Met/Met variants, Barbey said. Those with the Val/Val variant also were significantly more impaired in “specific competencies for intelligence like verbal comprehension, perceptual organization, working memory and processing speed,” he said.
To test these results, the researchers did the analysis over again “in a subset of individuals who had very similar (brain injuries) to the other group,” Barbey said. “We found the same kind of effects, suggesting that lesion location isn’t a factor influencing the difference between the groups.”
The finding opens a new avenue of exploration for treatments to aid the process of recovery from TBI, Barbey said.
Remember that sound bite you heard on the radio this morning? The grocery items your spouse asked you to pick up? Chances are, you won’t.
Researchers at the University of Iowa have found that when it comes to memory, we don’t remember things we hear nearly as well as things we see or touch.
“As it turns out, there is merit to the Chinese proverb ‘I hear, and I forget; I see, and I remember,” says lead author of the study and UI graduate student, James Bigelow.
“We tend to think that the parts of our brain wired for memory are integrated. But our findings indicate our brain may use separate pathways to process information. Even more, our study suggests the brain may process auditory information differently than visual and tactile information, and alternative strategies—such as increased mental repetition—may be needed when trying to improve memory,” says Amy Poremba, associate professor in the UI Department of Psychology and corresponding author on the paper, published this week in the journal PLoS One.
Bigelow and Poremba discovered that when more than 100 UI undergraduate students were exposed to a variety of sounds, visuals, and things that could be felt, the students were least apt to remember the sounds they had heard.
In an experiment testing short-term memory, participants were asked to listen to pure tones they heard through headphones, look at various shades of red squares, and feel low-intensity vibrations by gripping an aluminum bar. Each set of tones, squares and vibrations was separated by time delays ranging from one to 32 seconds.
Although students’ memory declined across the board when time delays grew longer, the decline was much greater for sounds, and began as early as four to eight seconds after being exposed to them.
While this seems like a short time span, it’s akin to forgetting a phone number that wasn’t written down, notes Poremba. “If someone gives you a number, and you dial it right away, you are usually fine. But do anything in between, and the odds are you will have forgotten it,” she says.
In a second experiment, Bigelow and Poremba tested participants’ memory using things they might encounter on an everyday basis. Students listened to audio recordings of dogs barking, watched silent videos of a basketball game, and touched and held common objects blocked from view, such as a coffee mug. The researchers found that between an hour and a week later, students were worse at remembering the sounds they had heard, but their memory for visual scenes and tactile objects was about the same.
Both experiments suggest that the way your mind processes and stores sound may be different from the way it process and stores other types of memories. And that could have big implications for educators, design engineers, and advertisers alike.
“As teachers, we want to assume students will remember everything we say. But if you really want something to be memorable you may need to include a visual or hands-on experience, in addition to auditory information,” says Poremba.
Previous research has suggested that humans may have superior visual memory, and that hearing words associated with sounds—rather than hearing the sounds alone—may aid memory. Bigelow and Poremba’s study builds upon those findings by confirming that, indeed, we remember less of what we hear, regardless of whether sounds are linked to words.
The study also is the first to show that our ability to remember what we touch is roughly equal to our ability to remember what we see. The finding is important, because experiments with nonhuman primates such as monkeys and chimpanzees have shown that they similarly excel at visual and tactile memory tasks, but struggle with auditory tasks. Based on these observations, the authors believe humans’ weakness for remembering sounds likely has its roots in the evolution of the primate brain.
A new University of British Columbia study identifies an important molecular change that occurs in the brain when we learn and remember.
Published this month in Nature Neuroscience, the research shows that learning stimulates our brain cells in a manner that causes a small fatty acid to attach to delta-catenin, a protein in the brain. This biochemical modification is essential in producing the changes in brain cell connectivity associated with learning, the study finds.
In animal models, the scientists found almost twice the amount of modified delta-catenin in the brain after learning about new environments. While delta-catenin has previously been linked to learning, this study is the first to describe the protein’s role in the molecular mechanism behind memory formation.
“More work is needed, but this discovery gives us a much better understanding of the tools our brains use to learn and remember, and provides insight into how these processes become disrupted in neurological diseases,” says co-author Shernaz Bamji, an associate professor in UBC’s Life Sciences Institute.
It may also provide an explanation for some mental disabilities, the researchers say. People born without the gene have a severe form of mental retardation called Cri-du-chat syndrome, a rare genetic disorder named for the high-pitched cat-like cry of affected infants. Disruption of the delta-catenin gene has also been observed in some patients with schizophrenia.
“Brain activity can change both the structure of this protein, as well as its function,” says Stefano Brigidi, first author of the article and a PhD candidate Bamji’s laboratory. “When we introduced a mutation that blocked the biochemical modification that occurs in healthy subjects, we abolished the structural changes in brain’s cells that are known to be important for memory formation.”
According to the researchers, more work is needed to fully establish the importance of delta-catenin in building the brain connectivity behind learning and memory. Disruptions to these nerve cell connections are also believed to cause neurodegenerative diseases such as Alzheimer’s and Huntington disease. Understanding the biochemical processes that are important for maintaining these connections may help address the abnormalities in nerve cells that occur in these disease states.
The electrical stimulation of the hippocampus in in-vivo experiments activates precisely the same receptor complexes as learning or memory recall. This has been discovered for the first time and the finding has now been published in the highly respected journal “Brain Structure Function”. “This may form the basis for the use of medications aimed at powering up dormant or less active memory cells,” says Gert Lubec, Head of Fundamental Research / Neuroproteomics at the University Department of Paediatrics and Adolescent Medicine at the MedUni Vienna.
“This discovery has far-reaching consequences both for the molecular understanding of memory formation and the understanding of the clinical electrical stimulation, which is already possible, of areas of the brain for therapeutic purposes,” says the MedUni Vienna researcher. Similar principles are currently already being used in the field of deep brain stimulation. With this technology, an implanted device delivers electronic impulses to the patient’s brain. This physical stimulation allows neuronal circuits to be influenced that control both behaviour and memory.
The latest findings very much form part of the highly controversial subject of “cognitive enhancement”. Scientists are currently discussing the possibility of improving mental capacity through the use of drugs - including in healthy subjects of all age groups, but especially in patients with age-related impairments of cognitive processes.
With regard to the study design, two electrodes were implanted into the brain in an animal model. One transferred electrical impulses to stimulate the hippocampus, while the other transferred the electrical signals away. “These electrical potentials are the electrical equivalent of memory and are known as LTP (Long Term Potentiation),” explains Lubec. The generation of LTP in an in-vivo experiment was accompanied by specific changes in the receptor complexes - the same receptor complexes that are also activated during learning and memory formation.
To answer the seemingly simple question “Have I been here before?” we must use our memories of previous experiences to determine if our current location is familiar or novel. In a new study published in the Journal of Neuroscience researchers from the RIKEN Brain Science Institute have identified a region of the hippocampus, called CA2, which is sensitive to even small changes in a familiar context. The results provide the first clue to the contributions of CA2 to memory and may help shed light on why this area is often found to be abnormal in the schizophrenic brain.
Change comes in many flavors; if we move to a new country, city or house it is easy to recognize the novelty of the environment, but if we come home to find the furniture rearranged or a new piece of art on the wall, this recognition may be much slower. Scientists believe this is because memory formation requires comparing current information with previous experience and the larger the overlap, the more difficult the distinction. It has long been known that the hippocampus is a region of the brain crucial for this type of memory, however the identification of neurons responsible for this comparison has remained elusive.
In this study Marie Wintzer, Roman Boehringer, Denis Polygalov and Thomas McHugh used genetically modified mice and advanced cell imaging techniques to demonstrate that while the entire hippocampus is capable of detecting large changes in context, the small and often overlooked CA2 region is exquisitely sensitive to small changes.
Mice were familiarized with one context and then placed either in a much different context or back in the original with small alterations, such as several new small objects. By detecting the expression of activity induced genes Wintzer and colleagues were able to demonstrate that just a few new objects in the otherwise unchanged context completely altered the pattern of active cells specifically in CA2. Mice that had been genetically engineered to lack this CA2 response explored the new context much less than their normal siblings.
“CA2 has often been overlooked or simply grouped together with its more prominent neighbors, but these data suggest it’s unique and important for recognizing and reacting to changes in our environments” explains Dr. McHugh, the leader of the study.
Compared to rodents, human CA2 is proportionally larger, but still as mysterious. One intriguing finding has been that early in the onset of schizophrenia and bipolar disorder there is a loss of inhibitory neurons specifically in CA2. In addition to the memory problems that accompany these diseases, patients often exhibit a hyper-sensitivity to changes in environment and routine. This study suggests there may be a functional relationship between this sensitivity and CA2 dysfunction, hinting at a new circuit to target in our attempts to understand the function of both the normal and diseased brain.