Posts tagged hippocampus
Articles and news from the latest research reports.
Neurons in the Brain Tune into Different Frequencies for Different Spatial Memory Tasks
Your brain transmits information about your current location and memories of past locations over the same neural pathways using different frequencies of a rhythmic electrical activity called gamma waves, report neuroscientists at The University of Texas at Austin.
The research, published in the journal Neuron on April 17, may provide insight into the cognitive and memory disruptions seen in diseases such as schizophrenia and Alzheimer’s, in which gamma waves are disturbed.
Previous research has shown that the same brain region is activated whether we’re storing memories of a new place or recalling past places we’ve been.
“Many of us leave our cars in a parking garage on a daily basis. Every morning, we create a memory of where we parked our car, which we retrieve in the evening when we pick it up,” said Laura Colgin, assistant professor of neuroscience and member of the Center for Learning and Memory in The University of Texas at Austin’s College of Natural Sciences. “How then do our brains distinguish between current location and the memory of a location? Our new findings suggest a mechanism for distinguishing these different representations.”
Memory involving location is stored in an area of the brain called the hippocampus. The neurons in the hippocampus that store spatial memories (such as the location where you parked your car) are called place cells. The same set of place cells are activated both when a new memory of a location is stored and, later, when the memory of that location is recalled or retrieved.
When the hippocampus forms a new spatial memory, it receives sensory information about your current location from a brain region called the entorhinal cortex. When the hippocampus recalls a past location, it retrieves the stored spatial memory from a subregion of the hippocampus called CA3.
The entorhinal cortex and CA3 transmit these different types of information using different frequencies of gamma waves. The entorhinal cortex uses fast gamma waves, which have a frequency of about 80 Hz (about the same frequency as a bass E note played on a piano). In contrast, CA3 sends its signals on slow gamma waves, which have a frequency of about 40 Hz.
Colgin and her colleagues hypothesized that fast gamma waves promote encoding of recent experiences, while slow gamma waves support memory retrieval.
They tested these hypotheses by recording gamma waves in the hippocampus, together with electrical signals from place cells, in rats navigating through a simple environment. They found that place cells represented the rat’s current location when cells were active on fast gamma waves. When cells were active on slow gamma waves, place cells represented locations in the direction that the rat was heading.
“These findings suggest that fast gamma waves promote current memory encoding, such as the memory of where we just parked,” said Colgin. “However, when we need to remember where we are going, like when finding our parked car later in the day, the hippocampus tunes into slow gamma waves.”
Because gamma waves are seen in many areas of the brain besides the hippocampus, Colgin’s findings may generalize beyond spatial memory. The ability for neurons to tune into different frequencies of gamma waves provides a way for the brain to traffic different types of information across the same neuronal circuits.
Colgin said one of the next steps in her team’s research will be to apply technologies that induce different types of gamma waves in rats performing memory tasks. She imagines that they will be able to improve new memory encoding by inducing fast gamma waves. Conversely, she expects that inducing slow gamma waves will be detrimental to the encoding of new memories. Those slow gamma waves should trigger old memories, which would interfere with new learning.
Eavesdropping on brain cell chatter
Everything we do — all of our movements, thoughts and feelings – are the result of neurons talking with one another, and recent studies have suggested that some of the conversations might not be all that private. Brain cells known as astrocytes may be listening in on, or even participating in, some of those discussions. But a new mouse study suggests that astrocytes might only be tuning in part of the time — specifically, when the neurons get really excited about something. This research, published in Neuron, was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
For a long time, researchers thought that the star-shaped astrocytes (the name comes from the Greek word for star) were simply support cells for the neurons.
It turns out that these cells have a number of important jobs, including providing nutrients and signaling molecules to neurons, regulating blood flow, and removing brain chemicals called neurotransmitters from the synapse. The synapse is the point of information transfer between two neurons. At this connection point, neurotransmitters are released from one neuron to affect the electrical properties of the other. Long arms of astrocytes are located next to synapses, where they can keep tabs on the conversations going on between neurons.
In recent years, it has been shown that astrocytes may also play a role in neuronal communication. When neurons release neurotransmitters, levels of calcium change within astrocytes. Calcium is critical for many processes, including release of molecules from the cell, and activation of a host of proteins within the cell. The role of this astrocytic calcium signaling for brain function remains a mystery.
In this study, Baljit S. Khakh, Ph.D., of the University of California, Los Angeles and his colleagues wanted to know when astrocytes responded to neuron activity with changes in their internal calcium levels. Using calcium indicator dyes, the researchers were able to image, for the first time, changes in calcium levels in the entire astrocyte. Previously, it was only possible to look at certain areas of the cell at one time, which provided an incomplete picture of what was happening.
Dr. Khakh said one of the most important outcomes of this work was in the methods that were used. “What our use of these calcium indicators shows is that we can image calcium throughout the entire astrocyte. This provides a new set of tools for the research community to use and to extend these findings,” he said.
“There has been intense interest in understanding how astrocytes facilitate communication between neurons, but it is only recently that studies with this level of precision have been possible,” said Edmund Talley, Ph.D., program director at NINDS. “Dr. Khakh’s study is an example of an exciting basic, or fundamental, research project that could have an important contribution to the shifting field of astrocyte biology,” he added.
For these experiments, researchers focused on the mossy fiber pathway, which connects two areas of the hippocampus, the structure involved in learning and memory. “This pathway has a unique architecture and although it has been very well studied, the role of astrocytes in this circuit has not been previously explored. This study provides one of the first really detailed understandings of astrocytes within this particular circuit,” said Dr. Khakh.
Dr. Khakh’s team activated neurons (getting them to release neurotransmitter by a variety of techniques) and then looked for a response in the neighboring astrocyte. As calcium levels rose, the astrocyte would light up quickly. They discovered that two neurotransmitters, glutamate and GABA, triggered the astrocytes to release calcium from their internal stores. Importantly, the researchers discovered that calcium levels increased through the entire astrocyte only if there was a large burst of neurotransmitter being released.
“We found that astrocytes in the mossy fiber pathway do not listen to the constant, millisecond by millisecond synaptic chatter that neurons engage in. Instead, they listen when neurons get excessively excited during bursts of activation,” said Dr. Khakh.
These findings suggest that astrocytes in the mossy fiber system may act as a switch that reacts to large amounts of neuronal activity by raising their levels of calcium. These calcium increases occur over multiple seconds, a relatively long time period compared to that seen in neurons. The spatial extent of the astrocyte calcium increases was also relatively large in comparison to the size of the synapse.
“Astrocytes may be sitting there quietly and when there is excessive activation in the neuronal circuit, they immediately respond with an increase in calcium which we could detect. And the next big question becomes, what they do with that calcium?” said Dr. Khakh.
Dr. Khakh’s results in the mossy fiber system differ from those others have described in other brain regions. This raises the intriguing possibility that astrocytes are not all the same and may serve various roles throughout the brain.
“It would be really interesting and important to find that astrocytes function differently in different areas of the brain, in a circuit-specific manner. This study gives a hint that this might be true,” said Dr. Talley.
How brain structures grow as memory develops
Our ability to store memories improves during childhood, associated with structural changes in the hippocampus and its connections with prefrontal and parietal cortices. New research from UC Davis is exploring how these brain regions develop at this crucial time. Eventually, that could give insights into disorders that typically emerge in the transition into and during adolescence and affect memory, such as schizophrenia and depression.
Located deep in the middle of the brain, the hippocampus plays a key role in forming memories. It looks something like two curving fingers branching forward from a common root. Each branch is a folded-over structure, with distinct areas in the upper and lower fold.
“For a long time it was assumed that the hippocampus didn’t develop at all after the first couple of years of life,” said Joshua Lee, a graduate student at the UC Davis Department of Psychology and Center for Mind and Brain. Improvements in memory were thought to be due entirely to changes in the brain’s outer layers, or cortex, that manage attention and strategies. But that picture has begun to change in the past five years.
Recently, Lee, Professor Simona Ghetti at the Center for Mind and Brain and Arne Ekstrom, assistant professor in the UC Davis Center for Neuroscience, used magnetic resonance imaging to map the hippocampus in 39 children aged eight to 14 years.
While subfields of the hippocampus have been mapped in adult humans and animal studies, it’s the first time that they have been measured in children, Ghetti said.
“This is really important to us, because it allows us to understand the heterogeneity along the hippocampus, which has been examined in human adults and other species” Ghetti said.
Looking at three subregions — the cornu ammonis (CA) 1, CA3/dentate gyrus and subiculum — they found that the first two expanded with age, with the most pronounced growth in the right hippocampus. Only in the oldest 25 percent of the children, within a few months either side of 14, did the sizes of all three regions decrease.
When they tested the children for memory performance, children with a larger CA3/dentate gyrus tended to perform better, they found. The work was published online March 15 by the journal Neuroimage.
In a related study in collaboration with the laboratory of Professor Silvia Bunge at UC Berkeley, published March 27 in Cerebral Cortex, the researchers also demonstrated how white matter connections projecting from the hippocampus to the brain cortex are related to memory function in children.
“White matter” tracts connect the prefrontal and parietal regions of the brain cortex, which control how we pay attention to things and engage in memory strategies, with the media-temporal lobe, the area that includes the hippocampus.
In the study, children performed a memory test that prompted them either to actively memorize an item — and therefore engage the prefrontal and parietal cortices — or to view an image passively. The ability to successfully modulate attention was linked to development of white matter tracts linking the prefrontal and parietal cortex tothe mediatemporal lobe, Ghetti said, but not to fronto-parietal connections.
Why your nose can be a pathfinder
When I was a child I used to sit in my grandfather’s workshop, playing with wood shavings. Freshly shaven wood has a distinct smell of childhood happiness, and whenever I get a whiff of that scent my brain immediately conjures up images of my grandfather at his working bench, the heat from the fireplace and the dog next to it.
Researchers at the Kavli Institute for Systems Neuroscience have recently discovered the process behind this phenomenon. The brain, it turns out, connects smells to memories through an associative process where neural networks are linked through synchronised brain waves of 20-40 Hz.
– We all know that smell is connected to memories, Kei Igarashi, lead author, explains.– We know that neurons in different brain regions need to oscillate in synchrony for these regions to speak effectively to each other. Still, the relationship between interregional coupling and formation of memory traces has remained poorly understood. So we designed a task to investigate how odour-place representation evolved in the entorhinal and hippocampal region, to figure out whether learning depends on coupling of oscillatory networks.
Smell guides the way in maze
The researchers designed a maze for rats, where a rat would see a hole to poke its nose into. When poking into the hole, the rat was presented with one of two alternative smells. One smell told the rat that food would be found in the left food cup behind the rat. The other smell told it that there was food in the right cup. The rat would soon learn which smell would lead to a reward where. After three weeks of training, the rats chose correctly on more than 85% of the trials. In order to see what happened inside the brain during acquisition, 16–20 electrode pairs were inserted in the hippocampus and in different areas of the entorhinal cortex.
After the associations between smell and place were well established, the researchers could see a pattern of brain wave activity (the electrical signal from a large number of neurons) during retrieval.
Coherent brain activity evolves with learning
– Immediately after the rat is exposed to the smell there is a burst in activity of 20–40 Hz waves in a specific connection between an area in the entorhinal cortex, lateral entorhinal cortex (LEC), and an area in the hippocampus, distal CA1 (dCA1), while a similar strong response was not observed in other connections, Igarashi explains.
This coherence of 20–40 Hz activity in the LEC and dCA1 evolved in parallel with learning, with little coherence between these areas before training started. By the time the learning period was over, cells were phase locked to the oscillation and a large portion of the cells responded specifically to one or the other of the smell-odour pairs.
Long distance communication in brain mediated by waves
– This is not the first time we observe that the brain uses synchronised wave activity to establish network connections, Edvard Moser, director of the Kavli Institute for Systems Neuroscience says. – Both during encoding and retrieval of declarative memories there is an interaction between these areas mediated through gamma and theta oscillations. However, this is the first study to relate the development of a specific band of oscillations to memory performance in the hippocampus. Together, the evidence is now piling up and pointing in the direction of cortical oscillations as a general mechanism for mediating interactions among functionally specialised neurons in distributed brain circuits.
So, there you have it – the signals from your nose translate and connect to memories in an orchestrated symphony of signals in your head. Each of these memories connects to a location, pinpointed on your inner map. So when you feel a wave of reminiscence triggered by a fragrance, think about how waves created this connection in the first place.
Scientists explain how memories stick together
Scientists at the Salk Institute have created a new model of memory that explains how neurons retain select memories a few hours after an event.
This new framework provides a more complete picture of how memory works, which can inform research into disorders liked Parkinson’s, Alzheimer’s, post-traumatic stress and learning disabilities.
"Previous models of memory were based on fast activity patterns," says Terrence Sejnowski, holder of Salk’s Francis Crick Chair and a Howard Hughes Medical Institute Investigator. "Our new model of memory makes it possible to integrate experiences over hours rather than moments."
Over the past few decades, neuroscientists have revealed much about how long-term memories are stored. For significant events—for example, being bit by a dog—a number of proteins are quickly made in activated brain cells to create the new memories. Some of these proteins linger for a few hours at specific places on specific neurons before breaking down.
This series of biochemical events allow us to remember important details about that event—such as, in the case of the dog bite, which dog, where it was located and so on.
One problem scientists have had with modeling memory storage is explaining why only selective details and not everything in that 1-2 hour window is strongly remembered. By incorporating data from previous literature, Sejnowski and first author Cian O’Donnell, a Salk postdoctoral researcher, developed a model that bridges findings from both molecular and systems observations of memory to explain how this 1-2 hour memory window works. The work is detailed in the latest issue of Neuron.
Using computational modeling, O’Donnell and Sejnowski show that, despite the proteins being available to a number of neurons in a given circuit, memories are retained when subsequent events activate the same neurons as the original event. The scientists found that the spatial positioning of proteins at both specific neurons and at specific areas around these neurons predicts which memories are recorded. This spatial patterning framework successfully predicts memory retention as a mathematical function of time and location overlap.
"One thing this study does is link what’s happing in memory formation at the cellular level to the systems level," says O’Donnell. "That the time window is important was already established; we worked out how the content could also determine whether memories were remembered or not. We prove that a set of ideas are consistent and sufficient to explain something in the real world."
The new model also provides a potential framework for understanding how generalizations from memories are processed during dreams.
While much is still unknown about sleep, research suggests that important memories from the day are often cycled through the brain, shuttled from temporary storage in the hippocampus to more long-term storage in the cortex. Researchers observed most of this memory formation in non-dreaming sleep. Little is known about if and how memory packaging or consolidation is done during dreams. However, O’Donnell and Sejnowski’s model suggests that some memory retention does happen during dreams.
"During sleep there’s a reorganizing of memory—you strengthen some memories and lose ones you don’t need anymore," says O’Donnell. "In addition, people learn abstractions as they sleep, but there was no idea how generalization processes happen at a neural level."
By applying their theoretical findings on overlap activity within the 1-2 hour window, they came up with a theoretical model for how the memory abstraction process might work during sleep.
(Source: salk.edu)
Neuroscientists Find Brain Activity May Mark the Beginning of Memories
By tracking brain activity when an animal stops to look around its environment, neuroscientists at Johns Hopkins University believe they can mark the birth of a memory.
Using lab rats on a circular track, James Knierim, professor of neuroscience in the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins, and a team of brain scientists, noticed that the rats frequently paused to inspect their environment with head movements as they ran. The scientists found that this behavior activated a place cell in their brain, which helps the animal construct a cognitive map, a pattern of activity in the brain that reflects the animal’s internal representation of its environment.
In a paper recently published in the journal Nature Neuroscience, the researchers state that when the rodents passed that same area of the track seconds later, place cells fired again, a neural acknowledgement that the moment has imprinted itself in the brain’s cognitive map in the hippocampus.
The hippocampus is the brain’s warehouse for long- and short-term processing of episodic memories, such as memories of a specific experience like a trip to Maine or a recent dinner. What no one knew was what happens in the hippocampus the moment an experience imprints itself as a memory.
“This is like seeing the brain form memory traces in real time,” said Knierim, senior author of the research. “Seeing for the first time the brain creating a spatial firing field tied to a specific behavioral experience suggests that the map can be updated rapidly and robustly to lay down a memory of that experience.”
A place cell is a type of neuron within the hippocampus that becomes active when an animal or human enters a particular place in its environment. The activation of the cells help create a spatial framework much like a map, that allows humans and animals to know where they are in any given location. Place cells can also act like neural flags that “mark” an experience on the map, like a pin that you drop on Google maps to mark the location of a restaurant.
“We believe that the spatial coordinates of the map are delivered to the hippocampus by one brain pathway, and the information about the things that populate the map, like the restaurant, are delivered by a separate pathway,” said Knierim. “When you experience a new item in the environment, the hippocampus combines these inputs to create a new spatial marker of that experience.”
In the experiments, researchers placed tiny wires in the brains of the rats to monitor when and where brain activity increased as they moved along the track in search of chocolate rewards. About every seven seconds, the rats stopped moving forward and turned their heads to the perimeter of the room as they investigated the different landmarks, a behavior called “head-scanning.”
“We found that many cells that were previously silent would suddenly start firing during a specific head-scanning event,” said Knierim. “On the very next lap around the track, many of these cells had a brand new place field at that exact same location and this place field remained usually for the rest of the laps. We believe that this new place field marks the site of the head scan and allows the brain to form a memory of what it was that the rat experienced during the head scan.”
Knierim said the formation and stability of place fields and the newly-activated place cells requires further study. The research is primarily intended to understand how memories are formed and retrieved under normal circumstances, but it could be applicable to learning more about people with brain trauma or hippocampal damage due to aging or Alzheimer’s.
“There are strong indications that humans and rats share the same spatial mapping functions of the hippocampus, and that these maps are intimately related to how we organize and store our memories of prior life events,” said Knierim. “Since the hippocampus and surrounding brain areas are the first parts of the brain affected in Alzheimer’s, we think that these studies may lend some insight into the severe memory loss that characterizes the early stages of this disease.”
(Image: Shutterstock)
Regular aerobic exercise boosts memory area of brain in older women
Regular aerobic exercise seems to boost the size of the area of the brain (hippocampus) involved in verbal memory and learning among women whose intellectual capacity has been affected by age, indicates a small study published online in the British Journal of Sports Medicine.
The hippocampus has become a focus of interest in dementia research because it is the area of the brain involved in verbal memory and learning, but it is very sensitive to the effects of ageing and neurological damage.
The researchers tested the impact of different types of exercise on the hippocampal volume of 86 women who said they had mild memory problems, known as mild cognitive impairment - and a common risk factor for dementia.
All the women were aged between 70 and 80 years old and were living independently at home.
Roughly equal numbers of them were assigned to either twice weekly hour long sessions of aerobic training (brisk walking); or resistance training, such as lunges, squats, and weights; or balance and muscle toning exercises, for a period of six months.
The size of their hippocampus was assessed at the start and the end of the six month period by means of an MRI scan, and their verbal memory and learning capacity was assessed before and afterward using a validated test (RAVLT).
Only 29 of the women had before and after MRI scans, but the results showed that the total volume of the hippocampus in the group who had completed the full six months of aerobic training was significantly larger than that of those who had lasted the course doing balance and muscle toning exercises.
No such difference in hippocampal volume was seen in those doing resistance training compared with the balance and muscle toning group.
However, despite an earlier finding in the same sample of women that aerobic exercise improved verbal memory, there was some evidence to suggest that an increase in hippocampal volume was associated with poorer verbal memory.
This suggests that the relationship between brain volume and cognitive performance is complex, and requires further research, say the authors.
But at the very least, aerobic exercise seems to be able to slow the shrinkage of the hippocampus and maintain the volume in a group of women who are at risk of developing dementia, they say.
And they recommend regular aerobic exercise to stave off mild cognitive decline, which is especially important, given the mounting evidence showing that regular exercise is good for cognitive function and overall brain health, and the rising toll of dementia.
Worldwide, one new case of dementia is diagnosed every four seconds, with the number of those afflicted set to rise to more than 115 million by 2050, they point out.
(Figure 1: Fluorescent labeling reveals mossy fibers (red) projecting from the dentate gyrus (green) into the CA2 subregion (orange). Credit: Keigo Kohara, RIKEN–MIT Center for Neural Circuit Genetics)
Novel combination of techniques reveals new details about the neuronal networks for memory
Learning and memory are believed to occur as a result of the strengthening of synaptic connections among neurons in a brain structure called the hippocampus. The hippocampus consists of five subregions, and a circuit formed between four of these is thought to be particularly important for memory formation. Keigo Kohara and colleagues from the RIKEN–MIT Center for Neural Circuit Genetics and RIKEN BioResource Center have now identified a previously unknown circuit involving the fifth subregion.
For a hundred years, memory research has typically focused on the main circuit, which projects from layer II of the entorhinal cortex via the dentate gyrus to subregion CA3 and then CA1. Subregion CA2 lies between CA3 and CA1 but its cells are less elaborate than those of its neighbors and were thought not to receive inputs from the dentate gyrus.
Kohara and his colleagues combined anatomical, genetic and physiological techniques to analyze the connections formed by neurons in the CA2 subregion of the hippocampus in unprecedented detail. First, they identified the CA2 subregion by examining the expression of three genes that encode proteins called RGS14, PCP4 and STEP using a fluorescent marker to label nerve fibers—a technique called fluorescent immunohistochemistry. They were surprised to discover that, contrary to expectations, CA2 neurons receive extensive inputs from cells in the dentate gyrus (Fig.1).
New clue to autism found inside brain cells
The problems people with autism have with memory formation, higher-level thinking and social interactions may be partially attributable to the activity of receptors inside brain cells, researchers at Washington University School of Medicine in St. Louis have learned.
(Image caption: Learning, social interactions and higher-level thinking in people with autism may be adversely affected by receptors inside brain cells, scientists at Washington University School of Medicine have learned. The type of receptor they studied glows green on the surface of this cell. Inside the cell, the receptor covers a membrane stained red. Credit: Yuh-Jiin I. Jong)
Scientists were already aware that the type of receptor in question was a potential contributor to these problems – when located on the surfaces of brain cells. Until now, though, the role of the same type of receptor located inside the cell had gone unrecognized. Such receptors inside cells significantly outnumber the same type of receptors on the surface of cells.
The receptor under study, known as the mGlu5 receptor, becomes activated when it binds to the neurotransmitter glutamate, which is associated with learning and memory. This leads to chain reactions that convert the glutamate’s signal into messages traveling inside the cell.
In the new study, scientists working with cells in a dish linked mGlu5 receptors inside cells to processes that turn down the volume at which brain cells talk to each other. These volume changes, essential for learning and memory, may become exaggerated in people with autism.
Pharmaceutical companies have developed therapeutic compounds to decrease signaling associated with the mGlu5 receptor, moderating its effects on brain cells’ volume knobs. But the compounds were designed to target mGlu5 surface receptors. In light of the new findings, the scientists question if those drugs will reach the receptors inside cells.
“Our results suggest that to have the greatest therapeutic benefit, we may need to make sure we’re blocking all of this type of receptor, both inside and on the surface of the cell,” said senior investigator Karen O’Malley, PhD, professor of neurobiology.
The findings, published March 25 in The Journal of Neuroscience, also add a significant new dimension to basic brain cell function. Scientists have long assumed that brain cell receptors are only active on the surface of cells. The new study shows that receptors can be active inside cells, and their effects can be considerably different from the same receptors located on the cell surface.
“The traditional wisdom was that receptors inside the cell were either waiting to go to work on the surface or had just finished working there,” said O’Malley. “But when we compared how much of the mGlu5 receptor was on the surface of cells to how much was inside it, we were seeing so much more receptor inside the cell – at least 50 percent, and in some cases as much as 90 percent – that we wondered if the interior receptors had separate functions.”
In earlier studies, O’Malley and her collaborators showed that mGlu5 receptors on the cell surface sent completely different messages than the same receptors inside the cell.
The scientists knew that most autism studies were conducted with compounds that blocked mGlu5 receptors but could not get into the cell. To determine whether blocking inside receptors would have different effects, O’Malley collaborated with Yukitoshi Izumi, MD, PhD, research professor of psychiatry, and Charles F. Zorumski, MD, the Samuel B. Guze Professor and head of the Department of Psychiatry, who study cell-based models of learning and memory.
When the scientists examined these model systems using compounds that allowed them to activate only mGlu5 receptors within cells, they found that these receptors played a bigger role in turning down the volume of brain cell communications than did the cell surface receptors.
In the last few years, scientists have found that 20 or more types of brain cell receptors located on cell surfaces also are present at high levels inside cells, O’Malley noted.
“This should be a factor we consider when we design drugs to target brain cell receptors,” she said. “Do we want to reach cell surface receptors, receptors inside the cell or both?”
(Source: news.wustl.edu)
Sensing subtle differences in the environment
The hippocampus is an important region of the brain that encodes spatial memory. It consists of a number of subfields that have specialized functions in memory storage and retrieval, but the precise role of some of the subfields remains unclear. Thomas McHugh and colleagues from the Laboratory for Circuit and Behavioral Physiology at the RIKEN Brain Science Institute have now discovered that in mice, the CA2 subfield senses small changes in the environment that are at odds with their spatial memory.
McHugh and his colleagues sought to determine the role of each subfield of the hippocampus in sensing familiar and new environments through a series of mouse experiments, focusing on the often overlooked CA2 subfield. They first exposed mice to a familiar environment, and then moved them back to their home cage. The researchers then either put the mice back in the first location or moved them to a new location that the mice had never experienced.
The research team examined similarities and differences in the way hippocampal subfields responded to the two environments by a procedure known as catFISH—cellular compartment analysis of temporal activity by fluorescence in situ hybridization. This technique allows the timing of neuronal activity to be determined and permits the assessment of contextual memory by observing changes in response to environmental manipulations.
The researchers found that in most cases, there was more overlap in the response of hippocampal neurons in all subfields when the mice were replaced in the first location after their time in the home cage compared with placement in the new location. However, in mice with a mutation in the CA3 subfield that causes CA3 neuronal activity to be uncoupled from the animal’s sensory environment, the change in CA2 response to a novel environment did not appear. The finding suggests that the CA3 inputs to CA2 modulate the ability of CA2 to sense novel environments.
In a final experiment, the researchers introduced more subtle changes to the environments during the second placement by taking objects from one location to the other. A distinct change in CA2 neuronal activity was found during these exposure intervals as a response to more subtle changes to the animals’ environment. The CA2 subfield may therefore be the most sensitive to subtle differences between existing memories and new experiences. “In future studies, we plan to use genetic approaches to control CA2 activity in order to understand its direct effect on behavior,” says McHugh.