Search PubMedSearch

Biomedical subjects

H Eichenbaum

Publications and source records attributed to H Eichenbaum.

At least 37 records · Page 2Linked to original sources

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

Functional organization of the hippocampal memory system.

In humans declarative or explicit memory is supported by the hippocampus and related structures of the medial temporal lobe working in concert with the cerebral cortex. This paper reviews our progress in developing an animal model for studies of cortical-hippocampal interactions in memory processing. Our findings support the view that the cortex maintains various forms of memory representation and that hippocampal structures extend the persistence and mediate the organization of these codings. Specifically, the parahippocampal region, through direct and reciprocal interconnections with the cortex, is sufficient to support the convergence and extended persistence of cortical codings. The hippocampus itself is critical to the organization cortical representations in terms of relationships among items in memory and in the flexible memory expression that is the hallmark of declarative memory.

Animals

Conservation of hippocampal memory function in rats and humans.

The hippocampus is critical to declarative memory in humans. This kind of memory involves associations among items or events that can be accessed flexibly to guide memory expression in various and even new situations. In animals, there has been controversy about whether the hippocampus is specialized for spatial memory or whether it mediates a general memory function, as it does in humans. To address this issue we trained normal rats and rats with hippocampal damage on non-spatial stimulus-stimulus associations, then probed the nature of their memory representations. We report here that normal rats demonstrated two forms of flexible memory expression, transitivity, the ability to judge inferentially across stimulus pairs that share a common element, and symmetry, the ability to associate paired elements presented in the reverse of training order. Rats with neurotoxic damage limited to the hippocampus demonstrated neither form of flexible expression, indicating that non-spatial declarative processing depends specifically on the hippocampus in animals as it does in humans.

Animals

Is the rodent hippocampus just for 'place'?

The prominent view that the rodent hippocampus is dedicated to spatial memory has been challenged recently by observations that both limit the nature of hippocampal spatial representation and extend its scope beyond literal space. These findings reveal that the rodent hippocampus mediates memory representations on the basis of non-spatial, as well as spatial, relations among items in memory, and supports access to these memories in a variety of situations. Therefore, the defining features of hippocampal representation in rodents, as in humans, lie not in the modality of the information processed, but in the organization of the information that supports a capacity for flexible memory expression.

Animals

Learning and memory for hierarchical relationships in the monkey: effects of aging.

Young and aged rhesus monkeys were tested on 2 versions of a transitive inference task measuring learning and memory for hierarchical relationships. Animals initially acquired 4 object discrimination problems arranged such that the relationship between the stimuli followed the hierarchy A > B > C > D > E. The second version of the task was similar but involved a series of 7 objects. Learning and memory for the hierarchical relationships were evaluated during probe trials in which novel pairs of nonadjacent items (e.g., B and D) were presented for a response. Standard task accuracy measures failed to distinguish young and aged subjects at any point in training. In contrast, response latency effects that are indicative of relational information processing in young monkeys were entirely absent in aged subjects. The findings highlight the value of a relational memory framework for establishing a detailed neuropsychological account of cognitive aging in the monkey.

Aging

Selective damage to the hippocampal region blocks long-term retention of a natural and nonspatial stimulus-stimulus association.

Normal rats rapidly acquire and remember associations between nonspatial stimuli as expressed in the social transmission of food preferences. In the present study, rats with selective neurotoxic lesions including all subdivisions of the hippocampal region (hippocampus proper, dentate gyrus, and subiculum) normally acquired and briefly retained the food odor association as demonstrated by intact memory immediately after social training. However, long-term memory in these animals was severely impaired in contrast to strong 24-h retention by intact rats. More selective lesions to the hippocampus proper plus dentate gyrus alone, or the subiculum alone had no effect on memory at either test interval. These findings indicate that the hippocampal region is required for long-term retention of a nonspatial form of natural memory.

Animals

Information coding in the rodent prefrontal cortex. I. Single-neuron activity in orbitofrontal cortex compared with that in pyriform cortex.

1. Extracellular spike activity was recorded from 1,942 single neurons in orbitofrontal cortex (OF) and 591 single neurons in pyriform cortex (PIR) over multiple sessions in rats performing an eight-odor discrimination task in which the stimulus sequence contained predictable associations between particular odor pairs. Neural firing patterns were examined in relation to task events in the current trial and variables associated with current sensory processing, events of recent past trials, and long-term associations involving the odor cues. 2. Overall, 34% of single neurons in OF and 30% of single neurons in PIR fired selectively during one or more salient trial events including trial initiation, odor sampling, performance of the discriminative response, and water consumption. The activity of other cells recorded in OF (13%) and PIR (10%) was suppressed for the duration of each trial. Although the proportion of some cell types differed between the two areas, the firing patterns of OF and PIR neurons were qualitatively indistinguishable. 3. Firing during odor sampling and the discriminative response was influenced by the identity of the current odor. Some cells fired selectively to a single odor, but most cells were coarsely tuned such that they fired to several of the eight odors to differing degrees consistent with previous reports. Considerable odor coding was observed in both OF and PIR. 4. Firing during trial initiation and odor sampling was also influenced by the identity and reward association of the odor presented in the immediately preceding trial. The influence of past odor identity and valence was observed in both OF and PIR. 5. Firing during trial events was also influenced by the acquired associations between odors and their assigned reward contingencies and between pairs of odors involved in predictive relationships. The reward valence of the current odor significantly influenced firing during odor sampling and the discriminative response; some cells responded preferentially to rewarded odors and others to nonrewarded odors. Firing during trial initiation and odor sampling reflected whether or not the odor in the current trial had been predicted by the odor in the preceding trial. In addition, firing during odor sampling reflected the expectation of reward in the following trial that could be inferred from the predictable associations between odors. Each of these properties was observed in both OF and PIR. 6. The findings in OF were consistent with the view that prefrontal subdivisions mediate the temporal organization of complex behaviors within specific informational domains. OF appears to be concerned with the specific domain of olfaction.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Information coding in the rodent prefrontal cortex. II. Ensemble activity in orbitofrontal cortex.

1. Neural activity was recorded from the orbitofrontal cortex (OF) of rats performing an eight-odor discrimination task that included predictable associations between particular odor pairs. A modified linear discriminant analysis was employed to characterize the population response in each trial of the task as a point in an N-dimensional activity space with the firing rate of each cell in the population represented on one of the N dimensions. The ability of the ensemble to discriminate among conditions of a variable was reflected in the tendency of population responses to cluster together in this activity space for repetitions of a given condition. We assessed coding of several variables describing the period of odor sampling, focusing on aspects of current, past, and future events reflected in single-neuron firing patterns, in ensembles composed of 22-138 cells active during the period when the rats sampled the discriminative stimulus in each trial. 2. OF ensembles performed well at discriminating variables with relevance to task demands represented in single-neuron firing patterns, specifically the physical attributes and assigned reward contingency of the current odor as well as the expectation of reward in the following trial that could be inferred from the predictable associations between particular pairs of odors. OF ensembles were able to correctly identify the identity and assigned reward contingency of the current odor in up to 52% (chance = 12.5%) and 99% (chance = 50%) of all trials, respectively, such that the observed behavioral performance required a population of 5,364 odor-responsive cells in the case of odor identity and only 40 cells in the case of valence. Expectations regarding upcoming rewards based on both assigned response contingency and associations between particular pairs of odors were correctly classified in up to 67% (chance = 20%) of all trials such that the observed level of behavioral performance required a population of 3,169 cells. 3. Other information represented in the single-neuron firing patterns, such as the identity and reward contingency of the preceding odor and specific odor-odor associations, was poorly encoded by OF ensembles. Thus neural ensembles in OF may represent only some of the information reflected in single-neuron activity. Stable coding of only the most useful and relevant information by the ensemble might emerge from the tuning properties of single neurons under the influence of the task at hand, producing in the well-trained animal the observed pattern of broad and diverse coding by single neurons and selective, task-relevant coding by neural ensembles in OF.

Animals

Correlates of hippocampal complex-spike cell activity in rats performing a nonspatial radial maze task.

The observation of hippocampal place cells forms a major line of evidence supporting the view that the hippocampus is dedicated to spatial processing. However, most studies demonstrating the spatial properties of hippocampal unit activity have employed tasks that emphasize spatial cues but minimize nonspatial cues. In the present experiment we recorded the activity of hippocampal complex-spike cells from rats performing a nonspatial radial maze task. Performance in this task was guided by local visual-tactile cues on the maze arms, while distal spatial cues were minimized and made irrelevant. The influence of three variables on unit activity was examined:type of cue on an arm, spatial location of an arm, and the relative position of the animal on an arm. Of the units recorded, almost one-fifth were classified as "cue cells" in that their activity was associated with cue type but not spatial location. Conversely, a similar proportion of the units were classified as "place cells" in that their activity was associated with location, but not cue type. In an additional similar proportion of units, firing was influenced only by relative position and not by local cues or spatial locations. For the majority of units, however, firing was related to combinations of these three variables, indicating that most hippocampal neurons encoded conjunctions or relations between spatial and local cue information. This pattern of results indicates that when local rather than distal spatial cues are emphasized, hippocampal neural activity is strongly influenced by salient nonspatial cues and shows no overwhelming predominance of place coding. These findings are at odds with the hypothesis that the hippocampus is selectively involved in spatial processing and, conversely, support the broader view that the hippocampus encodes both spatial and nonspatial relations among important experimental variables.

Action Potentials