Neuroscience

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Posts tagged place cells

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Activity in dendrites is critical in memory formation Why do we remember some things and not others? In a unique imaging study, two Northwestern University researchers have discovered how neurons in the brain might allow some experiences to be remembered while others are forgotten. It turns out, if you want to remember something about your environment, you better involve your dendrites. Using a high-resolution, one-of-a-kind microscope, Daniel A. Dombeck and Mark E. J. Sheffield peered into the brain of a living animal and saw exactly what was happening in individual neurons called place cells as the animal navigated a virtual reality maze. The scientists found that, contrary to current thought, the activity of a neuron’s cell body and its dendrites can be different. They observed that when cell bodies were activated but the dendrites were not activated during an animal’s experience, a lasting memory of that experience was not formed by the neurons. This suggests that the cell body seems to represent ongoing experience, while dendrites, the treelike branches of a neuron, help to store that experience as a memory. "There are a lot of theories on memory but very little data as to how individual neurons actually store information in a behaving animal," said Dombeck, assistant professor of neurobiology in the Weinberg College of Arts and Sciences and the study’s senior author. "Now we have uncovered signals in dendrites that we think are very important for learning and memory. Our findings could explain why some experiences are remembered and others are forgotten." In the brain’s hippocampus, there are hundreds of thousands of place cells — neurons essential to the brain’s GPS system. Dombeck and Sheffield are the first to image the activity of individual dendrites in place cells. Their findings contribute to our understanding of how the brain represents the world around it and also point to dendrites as a new potential target for therapeutics to combat memory deficits and debilitating diseases, such as Alzheimer’s disease (AD). Disruption to the brain’s GPS system is one of the first symptoms of AD, with many patients unable to find their way home. Understanding how place cells and their dendrites store these types of memories could help us find new ways to treat the disease. The Northwestern study will be published Oct. 26 by the journal Nature. Neuroscientist John O’Keefe discovered place cells in 1971 (and received this year’s Nobel Prize in physiology and medicine), but it is only in the last few years that scientists, such as Dombeck and Sheffield, have been able to image these neurons that represent a map of where we are in our environment. In their study, Dombeck and Sheffield found dendrite signals that could explain how an animal can experience something without storing the experience as a memory. They saw that dendrites are not always activated when the cell body is activated in a neuron. Signals produced in the dendrites (used to store information) and signals within the neuron cell body (used to compute and transmit information) can be either highly synchronized or desynchronized depending on how well the neurons remember different features of the maze. Scientists have long believed that the neuronal tasks of computing and storing information are connected — when neurons compute information, they are also storing it, and vice versa. The Northwestern study provides evidence against this classic view of neuronal function. "We experience events all the time, which must be represented in the brain by the activity of neurons, but not all these events can be recalled later," said Mark E. J. Sheffield, a postdoctoral fellow in Dombeck’s lab and first author of the study. "A daily commute to work, for example, requires the activity of millions of neurons, but you would be hard pressed to remember what was happening halfway through your commute last Tuesday," Sheffield said. "How is it then that the neurons could be activated during the commute without storing that information in the brain? Now we may have an explanation for how this occurs." Dombeck and Sheffield built their own laser scanning microscope that can image neurons on multiple planes. They then studied individual animals navigating (on a trackball) a virtual reality maze constructed using the video game Quake II. Each lit-up structure seen in the images they took indicate a neuron firing action potentials. The activity of these neurons represents an animal’s experience of where it is in the environment, the researchers said. Whether the neurons store this experience or not appears to depend on the activity of the neurons’ dendrites. (Image credit)

Activity in dendrites is critical in memory formation

Why do we remember some things and not others? In a unique imaging study, two Northwestern University researchers have discovered how neurons in the brain might allow some experiences to be remembered while others are forgotten. It turns out, if you want to remember something about your environment, you better involve your dendrites.

Using a high-resolution, one-of-a-kind microscope, Daniel A. Dombeck and Mark E. J. Sheffield peered into the brain of a living animal and saw exactly what was happening in individual neurons called place cells as the animal navigated a virtual reality maze.

The scientists found that, contrary to current thought, the activity of a neuron’s cell body and its dendrites can be different. They observed that when cell bodies were activated but the dendrites were not activated during an animal’s experience, a lasting memory of that experience was not formed by the neurons. This suggests that the cell body seems to represent ongoing experience, while dendrites, the treelike branches of a neuron, help to store that experience as a memory.

"There are a lot of theories on memory but very little data as to how individual neurons actually store information in a behaving animal," said Dombeck, assistant professor of neurobiology in the Weinberg College of Arts and Sciences and the study’s senior author. "Now we have uncovered signals in dendrites that we think are very important for learning and memory. Our findings could explain why some experiences are remembered and others are forgotten."

In the brain’s hippocampus, there are hundreds of thousands of place cells — neurons essential to the brain’s GPS system. Dombeck and Sheffield are the first to image the activity of individual dendrites in place cells.

Their findings contribute to our understanding of how the brain represents the world around it and also point to dendrites as a new potential target for therapeutics to combat memory deficits and debilitating diseases, such as Alzheimer’s disease (AD). Disruption to the brain’s GPS system is one of the first symptoms of AD, with many patients unable to find their way home. Understanding how place cells and their dendrites store these types of memories could help us find new ways to treat the disease.

The Northwestern study will be published Oct. 26 by the journal Nature.

Neuroscientist John O’Keefe discovered place cells in 1971 (and received this year’s Nobel Prize in physiology and medicine), but it is only in the last few years that scientists, such as Dombeck and Sheffield, have been able to image these neurons that represent a map of where we are in our environment.

In their study, Dombeck and Sheffield found dendrite signals that could explain how an animal can experience something without storing the experience as a memory.

They saw that dendrites are not always activated when the cell body is activated in a neuron. Signals produced in the dendrites (used to store information) and signals within the neuron cell body (used to compute and transmit information) can be either highly synchronized or desynchronized depending on how well the neurons remember different features of the maze.

Scientists have long believed that the neuronal tasks of computing and storing information are connected — when neurons compute information, they are also storing it, and vice versa. The Northwestern study provides evidence against this classic view of neuronal function.

"We experience events all the time, which must be represented in the brain by the activity of neurons, but not all these events can be recalled later," said Mark E. J. Sheffield, a postdoctoral fellow in Dombeck’s lab and first author of the study.

"A daily commute to work, for example, requires the activity of millions of neurons, but you would be hard pressed to remember what was happening halfway through your commute last Tuesday," Sheffield said. "How is it then that the neurons could be activated during the commute without storing that information in the brain? Now we may have an explanation for how this occurs."

Dombeck and Sheffield built their own laser scanning microscope that can image neurons on multiple planes. They then studied individual animals navigating (on a trackball) a virtual reality maze constructed using the video game Quake II.

Each lit-up structure seen in the images they took indicate a neuron firing action potentials. The activity of these neurons represents an animal’s experience of where it is in the environment, the researchers said. Whether the neurons store this experience or not appears to depend on the activity of the neurons’ dendrites.

(Image credit)

Filed under place cells memory formation dendrites hippocampus neurons neuroscience science

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The Nobel Assembly at Karolinska Institutet has decided to award the 2014 Nobel Prize in Physiology or Medicine with one half to John O´Keefe and the other half jointly to May-Britt Moser and Edvard I. Moser for their discoveries of cells that constitute a positioning system in the brain.

How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? This year´s Nobel Laureates have discovered a positioning system, an “inner GPS” in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function.

In 1971, John O´Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus that was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. O´Keefe concluded that these “place cells” formed a map of the room.

More than three decades later, in 2005, May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells”, that generate a coordinate system and allow for precise positioning and pathfinding. Their subsequent research showed how place and grid cells make it possible to determine position and to navigate.

The discoveries of John O´Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?

How do we experience our environment?

The sense of place and the ability to navigate are fundamental to our existence. The sense of place gives a perception of position in the environment. During navigation, it is interlinked with a sense of distance that is based on motion and knowledge of previous positions.

Questions about place and navigation have engaged philosophers and scientists for a long time. More than 200 years ago, the German philosopher Immanuel Kant argued that some mental abilities exist as a priori knowledge, independent of experience. He considered the concept of space as an inbuilt principle of the mind, one through which the world is and must be perceived. With the advent of behavioural psychology in the mid-20th century, these questions could be addressed experimentally. When Edward Tolman examined rats moving through labyrinths, he found that they could learn how to navigate, and proposed that a “cognitive map” formed in the brain allowed them to find their way. But questions still lingered - how would such a map be represented in the brain?

John O´Keefe and the place in space

John O´Keefe was fascinated by the problem of how the brain controls behaviour and decided, in the late 1960s, to attack this question with neurophysiological methods. When recording signals from individual nerve cells in a part of the brain called the hippocampus, in rats moving freely in a room, O’Keefe discovered that certain nerve cells were activated when the animal assumed a particular place in the environment (Figure 1). He could demonstrate that these “place cells” were not merely registering visual input, but were building up an inner map of the environment. O’Keefe concluded that the hippocampus generates numerous maps, represented by the collective activity of place cells that are activated in different environments. Therefore, the memory of an environment can be stored as a specific combination of place cell activities in the hippocampus.

May-Britt and Edvard Moser find the coordinates

May-Britt and Edvard Moser were mapping the connections to the hippocampus in rats moving in a room when they discovered an astonishing pattern of activity in a nearby part of the brain called the entorhinal cortex. Here, certain cells were activated when the rat passed multiple locations arranged in a hexagonal grid (Figure 2). Each of these cells was activated in a unique spatial pattern and collectively these “grid cells” constitute a coordinate system that allows for spatial navigation. Together with other cells of the entorhinal cortex that recognize the direction of the head and the border of the room, they form circuits with the place cells in the hippocampus. This circuitry constitutes a comprehensive positioning system, an inner GPS, in the brain (Figure 3).

A place for maps in the human brain

Recent investigations with brain imaging techniques, as well as studies of patients undergoing neurosurgery, have provided evidence that place and grid cells exist also in humans. In patients with Alzheimer´s disease, the hippocampus and entorhinal cortex are frequently affected at an early stage, and these individuals often lose their way and cannot recognize the environment. Knowledge about the brain´s positioning system may, therefore, help us understand the mechanism underpinning the devastating spatial memory loss that affects people with this disease.

The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialized cells work together to execute higher cognitive functions. It has opened new avenues for understanding other cognitive processes, such as memory, thinking and planning.

(Source: nobelprize.org)

Filed under nobel prize John O´Keefe May-Britt Moser Edvard I. Moser hippocampus place cells entorhinal cortex grid cells medicine neuroscience science

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How the Brain Makes Sense of Spaces, Large and Small When an animal encounters a new environment, the neurons in its brain that are responsible for mapping out the space are ready for anything. So says a new study in which scientists at the Howard Hughes Medical Institute’s Janelia Research Campus examined neuronal activity in rats as they explored an unusually large maze for the first time. The researchers found that neurons in the brain’s hippocampus, where information about people, places, and events is stored, each contribute to an animal’s mental map at their own rate. Some neurons begin to associate themselves with the new space immediately, while others hold back, contributing only if the space expands beyond a size that can be represented by the first-line neurons. Similar mechanisms may be at play as the human brain records a new experience, says Janelia group leader Albert Lee, who led the study. Lee, graduate student Dylan Rich, and Hua Peng-Liaw, a technician in Lee’s lab, published their findings in the August 15, 2014, issue of the journal Science. “The hippocampus has to represent arbitrary things,” Lee says. “When a new experience begins, we don’t know how long it’s going to last, and the brain has to form a new representation on the fly. This mechanism means that the hippocampus doesn’t have to adjust its representation if an environment is larger than predicted, or if an experience goes on longer than expected.” As an animal explores a new environment, cells in its hippocampus fire to mark new places that it encounters. The cells, called place cells, fire randomly, but become associated with the shapes, smells, and other sensory cues present in that location. In humans, analogous cells store memories of people, places, facts, and events. In rodents, about a third of the cells in the region of the hippocampus devoted to spatial learning participate in mapping a typical laboratory-sized maze. Different mazes are represented by different but overlapping sets of neurons. The differences between those sets allow the brain to distinguish between memories of different environments. But what happens when an animal finds itself in an environment larger than a five-meter laboratory maze? In the wild, rats can traverse territories as long as 50 meters. Lee wanted to know how the hippocampus kept track of environments that placed greater demands on its neurons. If cells continued to mark off space at the rate that scientists had observed in more confined environments, the animal’s mental map would quickly lose its uniqueness. “If every cell is active in the representation of a single space, then you can’t use this mechanism to distinguish memories of different things,” Lee points out.  So Lee and his team stocked up on supplies from the hardware store and built their own maze, far larger than any that had been used previously to track place cell activity. The 48-meter maze wouldn’t fit inside Lee’s lab, so Lee, Rich, and Liaw set it up in a large cage-cleaning room at Janelia. The room was busy during the week, so the team did their experiments on weekends. For multiple weekends over the course of about two years, Janelia’s vivarium staff would clear the room for them, and then the team would reassemble the maze and set up video cameras and electrophysiology equipment. The team recorded the activity of individual cells in the hippocampus as rats explored the maze for the first time. They first introduced the animals to a small portion of the maze, then gradually increased the territory to which the rats had access, monitoring how the brain added new information to its spatial map. When the scientists analyzed their data, they discovered that from the time the rats entered the maze, their brains were ready to represent an environment of any size. “Instead of the hippocampus having to adjust in time as the animal notices that the maze gets larger, it anticipates all different sizes of mazes from the beginning,” Lee says. “It does this by dividing up its population of neurons so that certain ones are ready to represent smaller mazes, others are ready to represent medium-size mazes, and others, large ones.” All of the neurons acted independently, firing randomly to mark off places in the maze. But some neurons had a greater propensity to mark off space than others, Lee explains. Some neurons mark space quickly and become associated with many places in the maze, whereas others are less likely to fire. These, Lee says, are reserved for mapping larger spaces. In small environments, a subset of the cells that are most likely to mark off space – those that have a chance to fire while the animal explores – form the map on their own. In larger mazes, all of the neurons with a high propensity to mark space are recruited to the mapping effort, meaning they cannot be used to distinguish the representation of one large maze from another. That’s when the neurons with a lower tendency to fire step in, randomly marking space in a distinct, identifying set. “There’s always a set of neurons that is just at the edge, where they are equally likely to represent any given environment versus not, regardless of what its size is,” Lee says. “Those are the neurons the brain can actually use to distinguish which environment its in.” The system means the brain never has to adjust its representation of an environment as it is being created, Lee says. “All neurons are marking space at their own preferred rate, so there doesn’t have to be a mechanism to say, ‘you should fire because this maze is large or this maze is small.’ The hippocampus is ready for anything at any moment.” Cells in the human brain may record events in a similar way, marking off time as an event unfolds without knowing how long it will continue, Lee says.

How the Brain Makes Sense of Spaces, Large and Small

When an animal encounters a new environment, the neurons in its brain that are responsible for mapping out the space are ready for anything. So says a new study in which scientists at the Howard Hughes Medical Institute’s Janelia Research Campus examined neuronal activity in rats as they explored an unusually large maze for the first time.

The researchers found that neurons in the brain’s hippocampus, where information about people, places, and events is stored, each contribute to an animal’s mental map at their own rate. Some neurons begin to associate themselves with the new space immediately, while others hold back, contributing only if the space expands beyond a size that can be represented by the first-line neurons. Similar mechanisms may be at play as the human brain records a new experience, says Janelia group leader Albert Lee, who led the study. Lee, graduate student Dylan Rich, and Hua Peng-Liaw, a technician in Lee’s lab, published their findings in the August 15, 2014, issue of the journal Science.

“The hippocampus has to represent arbitrary things,” Lee says. “When a new experience begins, we don’t know how long it’s going to last, and the brain has to form a new representation on the fly. This mechanism means that the hippocampus doesn’t have to adjust its representation if an environment is larger than predicted, or if an experience goes on longer than expected.”

As an animal explores a new environment, cells in its hippocampus fire to mark new places that it encounters. The cells, called place cells, fire randomly, but become associated with the shapes, smells, and other sensory cues present in that location. In humans, analogous cells store memories of people, places, facts, and events.

In rodents, about a third of the cells in the region of the hippocampus devoted to spatial learning participate in mapping a typical laboratory-sized maze. Different mazes are represented by different but overlapping sets of neurons. The differences between those sets allow the brain to distinguish between memories of different environments.

But what happens when an animal finds itself in an environment larger than a five-meter laboratory maze? In the wild, rats can traverse territories as long as 50 meters. Lee wanted to know how the hippocampus kept track of environments that placed greater demands on its neurons.

If cells continued to mark off space at the rate that scientists had observed in more confined environments, the animal’s mental map would quickly lose its uniqueness. “If every cell is active in the representation of a single space, then you can’t use this mechanism to distinguish memories of different things,” Lee points out. 

So Lee and his team stocked up on supplies from the hardware store and built their own maze, far larger than any that had been used previously to track place cell activity. The 48-meter maze wouldn’t fit inside Lee’s lab, so Lee, Rich, and Liaw set it up in a large cage-cleaning room at Janelia.

The room was busy during the week, so the team did their experiments on weekends. For multiple weekends over the course of about two years, Janelia’s vivarium staff would clear the room for them, and then the team would reassemble the maze and set up video cameras and electrophysiology equipment. The team recorded the activity of individual cells in the hippocampus as rats explored the maze for the first time. They first introduced the animals to a small portion of the maze, then gradually increased the territory to which the rats had access, monitoring how the brain added new information to its spatial map.

When the scientists analyzed their data, they discovered that from the time the rats entered the maze, their brains were ready to represent an environment of any size. “Instead of the hippocampus having to adjust in time as the animal notices that the maze gets larger, it anticipates all different sizes of mazes from the beginning,” Lee says. “It does this by dividing up its population of neurons so that certain ones are ready to represent smaller mazes, others are ready to represent medium-size mazes, and others, large ones.”

All of the neurons acted independently, firing randomly to mark off places in the maze. But some neurons had a greater propensity to mark off space than others, Lee explains. Some neurons mark space quickly and become associated with many places in the maze, whereas others are less likely to fire. These, Lee says, are reserved for mapping larger spaces.

In small environments, a subset of the cells that are most likely to mark off space – those that have a chance to fire while the animal explores – form the map on their own. In larger mazes, all of the neurons with a high propensity to mark space are recruited to the mapping effort, meaning they cannot be used to distinguish the representation of one large maze from another. That’s when the neurons with a lower tendency to fire step in, randomly marking space in a distinct, identifying set.

“There’s always a set of neurons that is just at the edge, where they are equally likely to represent any given environment versus not, regardless of what its size is,” Lee says. “Those are the neurons the brain can actually use to distinguish which environment its in.”

The system means the brain never has to adjust its representation of an environment as it is being created, Lee says. “All neurons are marking space at their own preferred rate, so there doesn’t have to be a mechanism to say, ‘you should fire because this maze is large or this maze is small.’ The hippocampus is ready for anything at any moment.”

Cells in the human brain may record events in a similar way, marking off time as an event unfolds without knowing how long it will continue, Lee says.

Filed under hippocampus neural activity place cells neurons memory neuroscience science

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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.

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.

Filed under gamma waves entorhinal cortex hippocampus memory place cells neuroscience science

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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)

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)

Filed under brain activity hippocampus memory place cells episodic memory neuroscience science

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In the brain, timing is everything Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow — suggesting that somehow, your brain had linked those two memories so that a fairly innocuous sound provokes dread. MIT neuroscientists have now discovered how two neural circuits in the brain work together to control the formation of such time-linked memories. This is a critical ability that helps the brain to determine when it needs to take action to defend against a potential threat, says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the Jan. 23 issue of Science. “It’s important for us to be able to associate things that happen with some temporal gap,” says Tonegawa, who is a member of MIT’s Picower Institute for Learning and Memory. “For animals it is very useful to know what events they should associate, and what not to associate.” The interaction of these two circuits allows the brain to maintain a balance between becoming too easily paralyzed with fear and being too careless, which could result in being caught off guard by a predator or other threat. The paper’s lead authors are Picower Institute postdocs Takashi Kitamura and Michele Pignatelli. Linking memories Memories of events, known as episodic memories, always contain three elements — what, where, and when. Those memories are created in a brain structure called the hippocampus, which must coordinate each of these three elements. To form episodic memories, the hippocampus also communicates with the region of the cerebral cortex just outside the hippocampus, known as the entorhinal cortex. The entorhinal cortex, which has several layers, receives sensory information, such as sights and sounds, from sensory processing areas of the brain and sends the information on to the hippocampus. Previous research has revealed a great deal about how the brain links the place and object components of memory. Certain neurons in the hippocampus, known as place cells, are specialized to fire when an animal is in a specific location, and also when the animal is remembering that location. However, when it comes to associating objects and time, “our understanding has fallen behind,” Tonegawa says. “Something is known, but relatively little compared to the object-place mechanism.” The new Science paper builds on a 2011 study from Tonegawa’s lab in which he identified a brain circuit necessary for mice to link memories of two events — a tone and a mild electric shock — that occur up to 20 seconds apart. This circuit connects layer 3 of the entorhinal cortex to the CA1 region of the hippocampus. When that circuit, known as the monosynaptic circuit, was disrupted, the animals did not learn to fear the tone. In the new paper, the researchers report the discovery of a previously unknown circuit that suppresses the monosynaptic circuit. This signal originates in a type of excitatory neurons discovered in Tonegawa’s lab, dubbed “island cells” because they form circular clusters within layer 2. Those cells stimulate inhibitory neurons in CA1 that suppress the set of excitatory CA1 neurons that are activated by the monosynaptic circuit. This circuit creates a counterbalance that limits the window of opportunity for two events to become linked. “This pathway might provide a mechanism for preventing constant learning of unimportant temporal associations,” says Michael Hasselmo, a professor of psychology at Boston University who was not part of the research team. The findings are “an important demonstration of the functional role of different populations of neurons in entorhinal cortex that provide input to the hippocampus,” Hasselmo adds. Deciphering circuits The researchers used optogenetics, a technology that allows specific populations of neurons to be turned on or off with light, to demonstrate the interplay of these two circuits. In normal mice, the maximum time gap between events that can be linked is about 20 seconds, but the researchers could lengthen that period by either boosting activity of layer 3 cells or suppressing layer 2 island cells. Conversely, they could shorten the window of opportunity by inhibiting layer 3 cells or stimulating input from layer 2 island cells, which both result in turning down CA1 activity. The researchers hypothesize that prolonged CA1 activity keeps the memory of the tone alive long enough so that it is still present when the shock takes place, allowing the two memories to be linked. They are now investigating whether CA1 neurons remain active throughout the entire gap between events.

In the brain, timing is everything

Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow — suggesting that somehow, your brain had linked those two memories so that a fairly innocuous sound provokes dread.

MIT neuroscientists have now discovered how two neural circuits in the brain work together to control the formation of such time-linked memories. This is a critical ability that helps the brain to determine when it needs to take action to defend against a potential threat, says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the Jan. 23 issue of Science.

“It’s important for us to be able to associate things that happen with some temporal gap,” says Tonegawa, who is a member of MIT’s Picower Institute for Learning and Memory. “For animals it is very useful to know what events they should associate, and what not to associate.”

The interaction of these two circuits allows the brain to maintain a balance between becoming too easily paralyzed with fear and being too careless, which could result in being caught off guard by a predator or other threat.

The paper’s lead authors are Picower Institute postdocs Takashi Kitamura and Michele Pignatelli.

Linking memories

Memories of events, known as episodic memories, always contain three elements — what, where, and when. Those memories are created in a brain structure called the hippocampus, which must coordinate each of these three elements.

To form episodic memories, the hippocampus also communicates with the region of the cerebral cortex just outside the hippocampus, known as the entorhinal cortex. The entorhinal cortex, which has several layers, receives sensory information, such as sights and sounds, from sensory processing areas of the brain and sends the information on to the hippocampus.

Previous research has revealed a great deal about how the brain links the place and object components of memory. Certain neurons in the hippocampus, known as place cells, are specialized to fire when an animal is in a specific location, and also when the animal is remembering that location. However, when it comes to associating objects and time, “our understanding has fallen behind,” Tonegawa says. “Something is known, but relatively little compared to the object-place mechanism.”

The new Science paper builds on a 2011 study from Tonegawa’s lab in which he identified a brain circuit necessary for mice to link memories of two events — a tone and a mild electric shock — that occur up to 20 seconds apart. This circuit connects layer 3 of the entorhinal cortex to the CA1 region of the hippocampus. When that circuit, known as the monosynaptic circuit, was disrupted, the animals did not learn to fear the tone.

In the new paper, the researchers report the discovery of a previously unknown circuit that suppresses the monosynaptic circuit. This signal originates in a type of excitatory neurons discovered in Tonegawa’s lab, dubbed “island cells” because they form circular clusters within layer 2. Those cells stimulate inhibitory neurons in CA1 that suppress the set of excitatory CA1 neurons that are activated by the monosynaptic circuit.

This circuit creates a counterbalance that limits the window of opportunity for two events to become linked. “This pathway might provide a mechanism for preventing constant learning of unimportant temporal associations,” says Michael Hasselmo, a professor of psychology at Boston University who was not part of the research team.

The findings are “an important demonstration of the functional role of different populations of neurons in entorhinal cortex that provide input to the hippocampus,” Hasselmo adds.

Deciphering circuits

The researchers used optogenetics, a technology that allows specific populations of neurons to be turned on or off with light, to demonstrate the interplay of these two circuits.

In normal mice, the maximum time gap between events that can be linked is about 20 seconds, but the researchers could lengthen that period by either boosting activity of layer 3 cells or suppressing layer 2 island cells. Conversely, they could shorten the window of opportunity by inhibiting layer 3 cells or stimulating input from layer 2 island cells, which both result in turning down CA1 activity.

The researchers hypothesize that prolonged CA1 activity keeps the memory of the tone alive long enough so that it is still present when the shock takes place, allowing the two memories to be linked. They are now investigating whether CA1 neurons remain active throughout the entire gap between events.

Filed under episodic memory hippocampus entorhinal cortex place cells neuroscience science

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Are we there yet? MIT researchers reveal how the brain keeps eyes on the prize. “Are we there yet?” As anyone who has traveled with young children knows, maintaining focus on distant goals can be a challenge. A new study from MIT suggests how the brain achieves this task, and indicates that the neurotransmitter dopamine may signal the value of long-term rewards. The findings may also explain why patients with Parkinson’s disease — in which dopamine signaling is impaired — often have difficulty in sustaining motivation to finish tasks. The work is described this week in the journal Nature. Previous studies have linked dopamine to rewards, and have shown that dopamine neurons show brief bursts of activity when animals receive an unexpected reward. These dopamine signals are believed to be important for reinforcement learning, the process by which an animal learns to perform actions that lead to reward. Taking the long view In most studies, that reward has been delivered within a few seconds. In real life, though, gratification is not always immediate: Animals must often travel in search of food, and must maintain motivation for a distant goal while also responding to more immediate cues. The same is true for humans: A driver on a long road trip must remain focused on reaching a final destination while also reacting to traffic, stopping for snacks, and entertaining children in the back seat. The MIT team, led by Institute Professor Ann Graybiel — who is also an investigator at MIT’s McGovern Institute for Brain Research — decided to study how dopamine changes during a maze task approximating work for delayed gratification. The researchers trained rats to navigate a maze to reach a reward. During each trial a rat would hear a tone instructing it to turn either right or left at an intersection to find a chocolate milk reward. Rather than simply measuring the activity of dopamine-containing neurons, the MIT researchers wanted to measure how much dopamine was released in the striatum, a brain structure known to be important in reinforcement learning. They teamed up with Paul Phillips of the University of Washington, who has developed a technology called fast-scan cyclic voltammetry (FSCV) in which tiny, implanted, carbon-fiber electrodes allow continuous measurements of dopamine concentration based on its electrochemical fingerprint. “We adapted the FSCV method so that we could measure dopamine at up to four different sites in the brain simultaneously, as animals moved freely through the maze,” explains first author Mark Howe, a former graduate student with Graybiel who is now a postdoc in the Department of Neurobiology at Northwestern University. “Each probe measures the concentration of extracellular dopamine within a tiny volume of brain tissue, and probably reflects the activity of thousands of nerve terminals.” Gradual increase in dopamine From previous work, the researchers expected that they might see pulses of dopamine released at different times in the trial, “but in fact we found something much more surprising,” Graybiel says: The level of dopamine increased steadily throughout each trial, peaking as the animal approached its goal — as if in anticipation of a reward. The rats’ behavior varied from trial to trial — some runs were faster than others, and sometimes the animals would stop briefly — but the dopamine signal did not vary with running speed or trial duration. Nor did it depend on the probability of getting a reward, something that had been suggested by previous studies. “Instead, the dopamine signal seems to reflect how far away the rat is from its goal,” Graybiel explains. “The closer it gets, the stronger the signal becomes.” The researchers also found that the size of the signal was related to the size of the expected reward: When rats were trained to anticipate a larger gulp of chocolate milk, the dopamine signal rose more steeply to a higher final concentration. In some trials the T-shaped maze was extended to a more complex shape, requiring animals to run further and to make extra turns before reaching a reward. During these trials, the dopamine signal ramped up more gradually, eventually reaching the same level as in the shorter maze. “It’s as if the animal were adjusting its expectations, knowing that it had further to go,” Graybiel says. An ‘internal guidance system’ “This means that dopamine levels could be used to help an animal make choices on the way to the goal and to estimate the distance to the goal,” says Terrence Sejnowski of the Salk Institute, a computational neuroscientist who is familiar with the findings but who was not involved with the study. “This ‘internal guidance system’ could also be useful for humans, who also have to make choices along the way to what may be a distant goal.” One question that Graybiel hopes to examine in future research is how the signal arises within the brain. Rats and other animals form cognitive maps of their spatial environment, with so-called “place cells” that are active when the animal is in a specific location. “As our rats run the maze repeatedly,” she says, “we suspect they learn to associate each point in the maze with its distance from the reward that they experienced on previous runs.” As for the relevance of this research to humans, Graybiel says, “I’d be shocked if something similar were not happening in our own brains.” It’s known that Parkinson’s patients, in whom dopamine signaling is impaired, often appear to be apathetic, and have difficulty in sustaining motivation to complete a long task. “Maybe that’s because they can’t produce this slow ramping dopamine signal,” Graybiel says. 

Are we there yet?

MIT researchers reveal how the brain keeps eyes on the prize.

“Are we there yet?”

As anyone who has traveled with young children knows, maintaining focus on distant goals can be a challenge. A new study from MIT suggests how the brain achieves this task, and indicates that the neurotransmitter dopamine may signal the value of long-term rewards. The findings may also explain why patients with Parkinson’s disease — in which dopamine signaling is impaired — often have difficulty in sustaining motivation to finish tasks.

The work is described this week in the journal Nature.

Previous studies have linked dopamine to rewards, and have shown that dopamine neurons show brief bursts of activity when animals receive an unexpected reward. These dopamine signals are believed to be important for reinforcement learning, the process by which an animal learns to perform actions that lead to reward.

Taking the long view

In most studies, that reward has been delivered within a few seconds. In real life, though, gratification is not always immediate: Animals must often travel in search of food, and must maintain motivation for a distant goal while also responding to more immediate cues. The same is true for humans: A driver on a long road trip must remain focused on reaching a final destination while also reacting to traffic, stopping for snacks, and entertaining children in the back seat.

The MIT team, led by Institute Professor Ann Graybiel — who is also an investigator at MIT’s McGovern Institute for Brain Research — decided to study how dopamine changes during a maze task approximating work for delayed gratification. The researchers trained rats to navigate a maze to reach a reward. During each trial a rat would hear a tone instructing it to turn either right or left at an intersection to find a chocolate milk reward.

Rather than simply measuring the activity of dopamine-containing neurons, the MIT researchers wanted to measure how much dopamine was released in the striatum, a brain structure known to be important in reinforcement learning. They teamed up with Paul Phillips of the University of Washington, who has developed a technology called fast-scan cyclic voltammetry (FSCV) in which tiny, implanted, carbon-fiber electrodes allow continuous measurements of dopamine concentration based on its electrochemical fingerprint.

“We adapted the FSCV method so that we could measure dopamine at up to four different sites in the brain simultaneously, as animals moved freely through the maze,” explains first author Mark Howe, a former graduate student with Graybiel who is now a postdoc in the Department of Neurobiology at Northwestern University. “Each probe measures the concentration of extracellular dopamine within a tiny volume of brain tissue, and probably reflects the activity of thousands of nerve terminals.”

Gradual increase in dopamine

From previous work, the researchers expected that they might see pulses of dopamine released at different times in the trial, “but in fact we found something much more surprising,” Graybiel says: The level of dopamine increased steadily throughout each trial, peaking as the animal approached its goal — as if in anticipation of a reward.

The rats’ behavior varied from trial to trial — some runs were faster than others, and sometimes the animals would stop briefly — but the dopamine signal did not vary with running speed or trial duration. Nor did it depend on the probability of getting a reward, something that had been suggested by previous studies.

“Instead, the dopamine signal seems to reflect how far away the rat is from its goal,” Graybiel explains. “The closer it gets, the stronger the signal becomes.” The researchers also found that the size of the signal was related to the size of the expected reward: When rats were trained to anticipate a larger gulp of chocolate milk, the dopamine signal rose more steeply to a higher final concentration.

In some trials the T-shaped maze was extended to a more complex shape, requiring animals to run further and to make extra turns before reaching a reward. During these trials, the dopamine signal ramped up more gradually, eventually reaching the same level as in the shorter maze. “It’s as if the animal were adjusting its expectations, knowing that it had further to go,” Graybiel says.

An ‘internal guidance system’

“This means that dopamine levels could be used to help an animal make choices on the way to the goal and to estimate the distance to the goal,” says Terrence Sejnowski of the Salk Institute, a computational neuroscientist who is familiar with the findings but who was not involved with the study. “This ‘internal guidance system’ could also be useful for humans, who also have to make choices along the way to what may be a distant goal.”

One question that Graybiel hopes to examine in future research is how the signal arises within the brain. Rats and other animals form cognitive maps of their spatial environment, with so-called “place cells” that are active when the animal is in a specific location. “As our rats run the maze repeatedly,” she says, “we suspect they learn to associate each point in the maze with its distance from the reward that they experienced on previous runs.”

As for the relevance of this research to humans, Graybiel says, “I’d be shocked if something similar were not happening in our own brains.” It’s known that Parkinson’s patients, in whom dopamine signaling is impaired, often appear to be apathetic, and have difficulty in sustaining motivation to complete a long task. “Maybe that’s because they can’t produce this slow ramping dopamine signal,” Graybiel says. 

Filed under dopamine parkinson's disease reinforcement learning place cells fast-scan cyclic voltammetry neuroscience science

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A neural code for navigation Neurons in the rat brain use a preexisting set of firing sequences to encode future navigational experiences Specialized neurons called place cells, located in the hippocampus region of the brain, fire when an animal is in a particular location in its environment, and it is the linear sequence of their firing that encodes in the brain movement trajectories from one location to another. Building on previous work, George Dragoi and Susumu Tonegawa from the RIKEN–MIT Center for Neural Circuit Genetics have now shown that place cells have a preexisting inventory of firing sequences that they can use to encode multiple novel routes of exploration. Specific sequences of place cells are known to encode spatial experiences, but it has been debated whether such sequences are formed during a new experience or preformed and adapted to specific experiences when required. Dragoi and Tonegawa recently showed that ‘future’ place cells fire in sequence while the animal is asleep, prior to experiencing a novel environment, and that animals use this preexisting neuronal firing pattern to rapidly learn how to navigate their surroundings. To confirm and investigate this mechanism further, the researchers first recorded the neuronal activity of place cells in rats during one hour of sleep. Next, they monitored this activity during movement along a track that the rat had not previously explored, and later recorded it during movement along the same track with two additional lengths separated by right-angle turns. They then correlated the temporal pattern of place cell activity recorded during sleep with the spatial pattern of activity recorded while the animals were freely exploring the longer track. The researchers found that the sequences of place cell activity were unique for each of the three lengths of the track and matched those recorded during sleep. “We had observed the same sequences as independent clusters of correlated temporal sequences during the preceding sleep period,” explains Dragoi.  The results suggest that rapid encoding of particular trajectories within novel environments is achieved during exploration by selecting from a set of preexisting temporal sequences that fired during sleep. In other words, hippocampal place cells appear to be prearranged into sets of sequential firing cells that can be adapted rapidly to encode for multiple spatial trajectories that the animal could undertake in its surroundings. Based on their data, Dragoi and Tonegawa predict that the sets of hippocampal place cells could encode for at least 15 unique future spatial experiences. In addition, their findings could explain the role that the hippocampus plays in humans in imagining future encounters within our own complex environment.

A neural code for navigation

Neurons in the rat brain use a preexisting set of firing sequences to encode future navigational experiences

Specialized neurons called place cells, located in the hippocampus region of the brain, fire when an animal is in a particular location in its environment, and it is the linear sequence of their firing that encodes in the brain movement trajectories from one location to another. Building on previous work, George Dragoi and Susumu Tonegawa from the RIKEN–MIT Center for Neural Circuit Genetics have now shown that place cells have a preexisting inventory of firing sequences that they can use to encode multiple novel routes of exploration.

Specific sequences of place cells are known to encode spatial experiences, but it has been debated whether such sequences are formed during a new experience or preformed and adapted to specific experiences when required. Dragoi and Tonegawa recently showed that ‘future’ place cells fire in sequence while the animal is asleep, prior to experiencing a novel environment, and that animals use this preexisting neuronal firing pattern to rapidly learn how to navigate their surroundings.

To confirm and investigate this mechanism further, the researchers first recorded the neuronal activity of place cells in rats during one hour of sleep. Next, they monitored this activity during movement along a track that the rat had not previously explored, and later recorded it during movement along the same track with two additional lengths separated by right-angle turns. They then correlated the temporal pattern of place cell activity recorded during sleep with the spatial pattern of activity recorded while the animals were freely exploring the longer track.

The researchers found that the sequences of place cell activity were unique for each of the three lengths of the track and matched those recorded during sleep. “We had observed the same sequences as independent clusters of correlated temporal sequences during the preceding sleep period,” explains Dragoi. 

The results suggest that rapid encoding of particular trajectories within novel environments is achieved during exploration by selecting from a set of preexisting temporal sequences that fired during sleep. In other words, hippocampal place cells appear to be prearranged into sets of sequential firing cells that can be adapted rapidly to encode for multiple spatial trajectories that the animal could undertake in its surroundings. Based on their data, Dragoi and Tonegawa predict that the sets of hippocampal place cells could encode for at least 15 unique future spatial experiences. In addition, their findings could explain the role that the hippocampus plays in humans in imagining future encounters within our own complex environment.

Filed under neuronal activity navigation place cells animal model hippocampus neuroscience science

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A “light switch” in the brain illuminates neural networks Researchers from NTNU’s Kavli Institute of Systems Neuroscience are able to see which cells communicate with each other in the brain by flipping a neural light switch. The results of their efforts are presented in an article in the 5 April issue of Science magazine. There are cells in your brain that recognize very specific places, and have that and nothing else as their job. These cells, called place cells, are found in an area behind your temple called the hippocampus. While these cells must be sent information from nearby cells to do their job, so far no one has been able to determine exactly what kind of cells work with place cells to craft the code they create for each location. Neurons come in many different types with specialized functions. Some respond to edges and borders, others to specific locations, others act like a compass and react to which way you turn your head. Now, researchers at the Kavli Institute for Systems Neuroscience have developed a range of advanced techniques that enable them to identify which neurons communicate with each other at different times in the rat brain, and in doing so, create the animal’s sense of direction. "A rat’s brain is the size of a grape. Inside there are about fifty million neurons that are connected together at a staggering 450 billion places (roughly)," explains Professor Edvard Moser, director of the Kavli Institute. "Inside this grape-sized brain are areas on each side that are smaller than a grape seed, where we know that memory and the sense of location reside. This is also where we find the neurons that respond to specific places, the place cells. But from which cells do these place cells get information?" From spaghetti to light switches The problem is, of course, that researchers cannot simply cut open the rat brain to see which cells have had contact. That would be the equivalent of taking a giant pile of cooked spaghetti, chopping it into little pieces, and then trying to figure out how the various spaghetti strands were tangled together before the pile was cut up. A job like this requires the use of a completely different set of neural tools, which is where the “light switches” come into play. Neurons share many similarities with electric cables when they send signals to each other. They send an electric current in one direction – from the “body” of the neuron and down a long arm, called the axon, which goes to another nerve cell next in line. Place cells thus get their small electric signals from a whole series of such arms. So how do light switches play into all of this?Viruses do the work “What we did first was to give these nerve arms a harmless viral infection,” Moser says. “We designed a unique virus that does not cause disease, but that acts as a pathway for delivering genes to specific cells. The virus creeps into the neurons, crawls up against the electric current, and uses the nerve cell’s own factory to make the genetic recipe that we gave to the virus to carry.” The genetic recipe enabled the cell to make the equivalent of a light switch. Our eyes actually contain the same kind of biological light switch, which allows us to see. The virus infection converts neurons that have previously existed only in darkness, deep inside the brain, to now be sensitive to light. Then the researchers inserted optical fibres in the rat’s brain to transmit light to the place cells that had light switches in them. They also implanted thin microelectrodes down between the cells so they could detect the signals sent through the axons every time the light from the optical fibre was turned on. "Now we had everything set up, with light switches installed in cells around the place cells, a lamp, and a way to record the activity," Moser said.10,000 times The researchers then turned the lights on and off more than ten thousand times in their rat lab partners, while they monitored and recorded the activity of hundreds of individual cells in the rats’ grape-sized brains. The researchers did this research while the rats ran around in a metre-square box, gathering treats. As the rats explored their box and found the treats, the researchers were able to use the light-sensitive cells to reveal how the rat’s brain created the map of where the rat had been. When the researchers put together all the information afterwards they concluded that there is a whole range of different specialized cells that together provide place cells their information. The brain’s GPS – its sense of place – is created by signals from head direction cells, border cells, cells that have no known function in creating location points and grid cells. Place cells receive both information about the rat’s surroundings and landmarks, but also continuously update their own movement, which is actually independent on sensory input. "The biggest mystery is the role that the cells that are not part of the sense of direction play. They send signals to place cells, but what do they actually do?" wonders Moser. "We also wonder how the cells in the hippocampus are able to sort out the various signals they receive. Do they ‘listen’ to all of the cells equally effectively all the time, or are there some cells that get more time than others to ‘talk’ to place cells?"

A “light switch” in the brain illuminates neural networks

Researchers from NTNU’s Kavli Institute of Systems Neuroscience are able to see which cells communicate with each other in the brain by flipping a neural light switch. The results of their efforts are presented in an article in the 5 April issue of Science magazine.

There are cells in your brain that recognize very specific places, and have that and nothing else as their job. These cells, called place cells, are found in an area behind your temple called the hippocampus. While these cells must be sent information from nearby cells to do their job, so far no one has been able to determine exactly what kind of cells work with place cells to craft the code they create for each location. Neurons come in many different types with specialized functions. Some respond to edges and borders, others to specific locations, others act like a compass and react to which way you turn your head.

Now, researchers at the Kavli Institute for Systems Neuroscience have developed a range of advanced techniques that enable them to identify which neurons communicate with each other at different times in the rat brain, and in doing so, create the animal’s sense of direction.

"A rat’s brain is the size of a grape. Inside there are about fifty million neurons that are connected together at a staggering 450 billion places (roughly)," explains Professor Edvard Moser, director of the Kavli Institute. "Inside this grape-sized brain are areas on each side that are smaller than a grape seed, where we know that memory and the sense of location reside. This is also where we find the neurons that respond to specific places, the place cells. But from which cells do these place cells get information?"

From spaghetti to light switches
The problem is, of course, that researchers cannot simply cut open the rat brain to see which cells have had contact. That would be the equivalent of taking a giant pile of cooked spaghetti, chopping it into little pieces, and then trying to figure out how the various spaghetti strands were tangled together before the pile was cut up.
A job like this requires the use of a completely different set of neural tools, which is where the “light switches” come into play.

Neurons share many similarities with electric cables when they send signals to each other. They send an electric current in one direction – from the “body” of the neuron and down a long arm, called the axon, which goes to another nerve cell next in line. Place cells thus get their small electric signals from a whole series of such arms.

So how do light switches play into all of this?

Viruses do the work
“What we did first was to give these nerve arms a harmless viral infection,” Moser says. “We designed a unique virus that does not cause disease, but that acts as a pathway for delivering genes to specific cells. The virus creeps into the neurons, crawls up against the electric current, and uses the nerve cell’s own factory to make the genetic recipe that we gave to the virus to carry.”

The genetic recipe enabled the cell to make the equivalent of a light switch. Our eyes actually contain the same kind of biological light switch, which allows us to see. The virus infection converts neurons that have previously existed only in darkness, deep inside the brain, to now be sensitive to light.

Then the researchers inserted optical fibres in the rat’s brain to transmit light to the place cells that had light switches in them. They also implanted thin microelectrodes down between the cells so they could detect the signals sent through the axons every time the light from the optical fibre was turned on.

"Now we had everything set up, with light switches installed in cells around the place cells, a lamp, and a way to record the activity," Moser said.

10,000 times
The researchers then turned the lights on and off more than ten thousand times in their rat lab partners, while they monitored and recorded the activity of hundreds of individual cells in the rats’ grape-sized brains. The researchers did this research while the rats ran around in a metre-square box, gathering treats. As the rats explored their box and found the treats, the researchers were able to use the light-sensitive cells to reveal how the rat’s brain created the map of where the rat had been.

When the researchers put together all the information afterwards they concluded that there is a whole range of different specialized cells that together provide place cells their information. The brain’s GPS – its sense of place – is created by signals from head direction cells, border cells, cells that have no known function in creating location points and grid cells. Place cells receive both information about the rat’s surroundings and landmarks, but also continuously update their own movement, which is actually independent on sensory input.

"The biggest mystery is the role that the cells that are not part of the sense of direction play. They send signals to place cells, but what do they actually do?" wonders Moser.

"We also wonder how the cells in the hippocampus are able to sort out the various signals they receive. Do they ‘listen’ to all of the cells equally effectively all the time, or are there some cells that get more time than others to ‘talk’ to place cells?"

Filed under brain place cells hippocampus nerve cells memory light switches neuroscience science

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