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H Eichenbaum

Publications and source records attributed to H Eichenbaum.

At least 19 recordsLinked to original sources

The global record of memory in hippocampal neuronal activity.

In humans the hippocampal region of the brain is crucial for declarative or episodic memory for a broad range of materials. In contrast, there has been controversy over whether the hippocampus mediates a similarly general memory function in other species, or whether it is dedicated to spatial memory processing. Evidence for the spatial view is derived principally from the observations of 'place cells'-hippocampal neurons that fire whenever the animal is in a particular location in its environment, or when it perceives a specific stimulus or performs a specific behaviour in a particular place. We trained rats to perform the same recognition memory task in several distinct locations in a rich spatial environment and found that the activity of many hippocampal neurons was related consistently to perceptual, behavioural or cognitive events, regardless of the location where these events occurred. These results indicate that nonspatial events are fundamental elements of hippocampal representation, and support the view that, across species, the hippocampus has a broad role in information processing associated with memory.

Animals

Crossmodal associative memory representations in rodent orbitofrontal cortex.

Firing patterns of neurons in the orbitofrontal cortex (OF) were analyzed in rats trained to perform a task that encouraged incidental associations between distinct odors and the places where their occurrence was detected. Many of the neurons fired differentially when the animals were at a particular location or sampled particular odors. Furthermore, a substantial fraction of the cells exhibited odor-specific firing patterns prior to odor presentation, when the animal arrived at a location associated with that odor. These findings suggest that neurons in the OF encode cross-modal associations between odors and locations within long-term memory.

Animals

Using olfaction to study memory.

In a series of studies we have been exploring the role of hippocampal function in memory using the model system of olfactory-hippocampal pathways and odor learning in rats. Our experiments show that hippocampus itself is not essential to memory for single odors, but is critical for forming the representations of relations among odor memories, and for the expression of odor memory representations in novel situations. These studies that exploit the exceptional qualities of olfactory learning are helping to clarify the nature of higher order memory processes in all mammals, and extending to declarative memory in humans.

Animals

Positional firing properties of perirhinal cortex neurons.

Neuronal activity in the perirhinal cortex was recorded while rats performed a spatial task on a four arm radial maze. The maze was defined by proximal multisensory cues on the arm surfaces and distal complex visual cues at the surround. During each recording session, rats were run in three conditions: baseline, a condition in which proximal and distal cues were manipulated, and a second baseline. Compared with the activity of hippocampal neurons in the same paradigm, a much smaller proportion of perirhinal neurons exhibited spatial selectivity and perirhinal place fields were larger than hippocampal place fields. Although perirhinal place fields exhibited a high degree of spatial tuning and reliability within a condition, they were not stable across conditions.

Animals

Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice.

Hippocampal "place cells" fire selectively when an animal is in a specific location. The fine-tuning and stability of place cell firing was compared in two types of mutant mice with different long-term potentiation (LTP) and place learning impairments. Place cells from both mutants showed decreased spatial selectivity. Place cell stability was also deficient in both mutants and, consistent with the severities in their LTP and spatial learning deficits, was more affected in mice with a point mutation [threonine (T) at position 286 mutated to alanine (A)] in the alpha calmodulin kinase II (alphaCaMKIIT286A) than in mice deficient for the alpha and Delta isoforms of adenosine 3'5'-monophosphate-responsive element binding proteins (CREBalphaDelta-). Thus, LTP appears to be important for the fine tuning and stabilization of place cells, and these place cell properties may be necessary for spatial learning.

Animals

The hippocampus as an associator of discontiguous events.

The hippocampus has long been thought to be an important cortical region for associative learning and memory. After several decades of experimental and theoretical studies, a picture is emerging slowly of the generic types of learning tasks that this neural structure might be essential for solving. Recently, there have been attempts to unify electrophysiological and behavioral observations from rodents performing spatial learning tasks with data from primates performing various tests of conditional and discrimination learning. Most of these theoretical frameworks have rested primarily on behavioral observations. Complementing these perspectives,we ask the question: given certain physiological constraints at the neuronal and cortical level, what class of learning problems is the hippocampus, in particular, most suited to solve? From a computational point of view, we argue that this structure is involved most critically in learning and memory tasks in which discontiguous items must be associated, in terms of their temporal or spatial positioning, or both.

Animals

Comparison of ventral subicular and hippocampal neuron spatial firing patterns in complex and simplified environments.

Activity from ventral subicular and hippocampal CA1 neurons was recorded in rats exploring a 4-arm radial maze in which the local and distal cues could be manipulated. Cells from both regions exhibited place fields, although ventral subicular neurons had larger fields than hippocampal cells. Rotation of the local and distal cues in opposite directions produced movement of the place fields in either direction or a complete change in firing pattern. Simplifying the environment also produced changes in place field location. Despite similarities between regions, subiculum fields decreased in size whereas hippocampal fields increased in the simple environment. These findings suggest that subicular cells may receive converging input from several hippocampal neurons and code more complex configurations of the cues.

Analysis of Variance

The hippocampus and transverse patterning guided by olfactory cues.

Normal rats and rats with hippocampal system damage were trained on a novel, olfactory version of the transverse-patterning task that involved the concurrent learning and continued performance of 3 partially ambiguous discrimination problems (A+B-, B+C-, C+A-). Animals with lesions of the fornix or perirhinal-entorhinal cortex acquired at least as rapidly as normal rats these problems presented in sequential blocks of trials involving the same stimulus pair. All groups also performed well on an initial test session when the order of stimulus pair presentations was randomized. Normal rats continued to discriminate appropriately in additional testing sessions with trials presented in random order. By contrast, both groups with hippocampal system damage performed poorly in continued random-order testing. These results extend the generality of the deficit in transverse patterning to the olfactory modality and demonstrate that the deficit is equivalent in magnitude after fornix or perirhinal-entorhinal damage. Findings also suggest that the transverse-patterning problem can be acquired transiently without critical hippocampal involvement, although continued performance relies on hippocampal function.

Analysis of Variance

Brain aging: changes in the nature of information coding by the hippocampus.

Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information.

Aging

Brain aging: impaired coding of novel environmental cues.

Studies of the spatial memory capacities of aged animals usually focus on performance during the learning of new environments. By contrast, efforts to characterize age-related alterations in spatial firing information processing by hippocampal neurons typically use an environment that is highly familiar to the animals. In the present study we compared the firing properties of hippocampal neurons in young adult and aged rats as they acquired spatial information about new environmental cues. Hippocampal complex spike cells were recorded while rats performed a radial arm maze task in a familiar environment and then recorded again after many of the spatial cues were changed. After the change in the environment, in aged rats 35-42% of place fields retained their original shape and location with respect to the maze center, although they usually rotated to another arm. By contrast, all place fields in young animals either disappeared or appeared in a new location. Some of the new place fields appeared in the new environment during the first 5 min of exploration, whereas others needed more than 30 min to develop fully. In the familiar environment spatial selectivity of place cells was similar in young and aged rats. By contrast, when rats were placed into a new environment, spatial selectivity decreased considerably in aged memory-impaired rats compared with that of young rats and aged rats with intact memory performance.

Aging

Memory representation within the parahippocampal region.

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

Animals

The hippocampus and memory for orderly stimulus relations.

Human declarative memory involves a systematic organization of information that supports generalizations and inferences from acquired knowledge. This kind of memory depends on the hippocampal region in humans, but the extent to which animals also have declarative memory, and whether inferential expression of memory depends on the hippocampus in animals, remains a major challenge in cognitive neuroscience. To examine these issues, we used a test of transitive inference pioneered by Piaget to assess capacities for systematic organization of knowledge and logical inference in children. In our adaptation of the test, rats were trained on a set of four overlapping odor discrimination problems that could be encoded either separately or as a single representation of orderly relations among the odor stimuli. Normal rats learned the problems and demonstrated the relational memory organization through appropriate transitive inferences about items not presented together during training. By contrast, after disconnection of the hippocampus from either its cortical or subcortical pathway, rats succeeded in acquiring the separate discrimination problems but did not demonstrate transitive inference, indicating that they had failed to develop or could not inferentially express the orderly organization of the stimulus elements. These findings strongly support the view that the hippocampus mediates a general declarative memory capacity in animals, as it does in humans.

Animals

Memory: old questions, new perspectives.

Studies with targeted mouse mutants are helping to clarify our understanding of cellular mechanisms that underlie memory. Now this approach is also providing tools for resolving controversies about cognitive processes in memory that have perplexed behavioral scientists for many years.

Animals

Discordance of spatial representation in ensembles of hippocampal place cells.

The extent to which small ensembles of neighboring hippocampal neurons alter their spatial firing patterns concurrently in response to stimulus manipulations was examined in young adult rats as well as in aged rats with and without memory impairment. Recordings from CA1 and CA3 cells were taken as rats performed a spatial radial-maze task that employed prominent distal visual stimuli attached to dark curtains surrounding the maze and local cues on each maze arm provided by inserts with distinctive visual, tactile, and olfactory stimuli. To test the influence of the different stimulus subsets, the distal and local cues were rotated 90 degrees in opposite directions (a Double Rotation). In response to this manipulation, place fields could maintain a fixed position to room coordinates, rotate with either the local or the distal cues, disappear, or new fields could appear. On average 79% of the cells within an ensemble responded in the same way, but only 37% of all ensembles were fully concordant. Typically discordant ensembles had place fields that rotated with one set of cues, whereas the other fields disappeared or new fields appeared. Ensembles in which the place fields rotated in two opposite directions were less frequent in young rats than would be expected by the occurrence of the individual responses, indicating selective competition between directly conflicting representations and ultimate suppression of one. These findings indicate that hippocampal neurons independently encode distinct subsets of the cues in a complex environment, although processing within the hippocampal network may actively reduce the simultaneous representation of conflicting orientation information. This kind of population activity might reflect the higher-order organization of new memories within an established knowledge framework or schema. Concordance was higher in aged memory-impaired rats than in young rats, and the suppression of conflicting representations was absent in these rats. These findings suggest that age-related memory impairment is at least in part associated with a decrease in the scope of information coded and in the coordination of encoded representations.

Animals

Cues that hippocampal place cells encode: dynamic and hierarchical representation of local and distal stimuli.

Hippocampal place fields were recorded as rats explored a four-arm radial maze surrounded by curtains holding distal stimuli and with distinct local tactile, olfactory, and visual cues covering each arm. Systematic manipulations of the individual cues and their interrelationships showed that different hippocampal neurons encoded individual local and distal cues, relationships among cues within a stimulus set, and the relationship between the local and distal cues. Double rotation trials, which maintained stimulus relationships within distal and local cue sets, but altered the relationship between them, often changed the responses of the sampled neural population and produced new representations. After repeated double rotation trials, the incidence of new representations increased, and the likelihood of a simple rotation with one of the cue sets diminished. Cue scrambling trials, which altered the topological relationship within the local or distal stimulus set, showed that the cells that followed one set of controlled stimuli responded as often to a single cue as to the constellation. These cells followed the single cue when the stimulus constellation was scrambled, but often continued firing in the same place when the stimulus was removed or switched to respond to other cues. When the maze was surrounded by a new stimulus configuration, all of the cells either developed new place fields or stopped firing, showing that the controlled stimuli had persistent and profound influence over hippocampal neurons. Together, the results show that hippocampal neurons encode a hierarchical representation of environmental information.

Animals

Declarative memory: insights from cognitive neurobiology.

The discovery of declarative memory as distinct from other forms of memory is a major recent achievement in cognitive science. Basic issues about the nature of declarative memory are considered in this review from the perspective of studies on its underlying brain mechanisms. These studies have shown that declarative memory is mediated by a specific brain system including areas of the cerebral cortex and hippocampal region that make distinct functional contributions to memory processing. These processing mechanisms mediate the organization of memories in ways that can support the special properties of declarative or explicit memory expression. Furthermore, the basic properties of declarative memory in human beings can be viewed as evolving from a capacity for organized memory representation and flexible memory expression in animals.

Animals