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H Eichenbaum

Publications and source records attributed to H Eichenbaum.

At least 55 records · Page 3Linked to original sources

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↗

Critical role of the parahippocampal region for paired-associate learning in rats.

Human amnesics are severely impaired in learning arbitrary associations between word pairs. This report examines the role of the hippocampal system in an analog of paired-associate learning developed for rats. Subjects with selective damage to the parahippocampal region and controls were tested on an odor-guided paired-associate task. Normal rats readily learned to distinguish paired associates from various mispairings of the same odors, whereas most animals with parahippocampal damage failed to learn. Lesioned animals were, however, able to acquire correct responses to stimulus pairs for which an association between odors was not required. These findings extend the usefulness of olfactory learning as a model for studies of higher order learning capacity in rodents and indicate that in rats, as in humans, hippocampal areas are critical for learning arbitrary nonspatial relationships between stimuli.

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Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: evidence for hippocampal processing in recognition memory.

Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused on cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus-evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stimuli stored in parahippocampal and neocortical structures.

Animals↗

Complementary roles of the orbital prefrontal cortex and the perirhinal-entorhinal cortices in an odor-guided delayed-nonmatching-to-sample task.

Continuing efforts toward designing odor-guided tasks for rats that are similar in memory demands to tasks used typically with primates have resulted in the development of a continuous delayed-nonmatching-to-sample (cDNM) task that is guided by olfactory stimuli. The results indicate that normal subjects acquire the cDNM task rapidly and that subsequent performance deteriorates with increases in memory delay or interitem interference. Moreover, different aspects of cDNM performance were shown to be differentially sensitive to selective lesions of the orbitofrontal and parahippocampal areas. Orbitofrontal cortex lesions disproportionately impaired cDNM acquisition; delay performance was impaired only under conditions of elevated levels of interitem interference. Combined perirhinal and entorhinal cortical lesions had no effect on cDNM acquisition but impaired cDNM performance at longer delays across all levels of interference. Fornix lesions did not impair either acquisition of cDNM or subsequent performance across long delays and increased interference. This pattern of impaired and spared capacities is similar to that observed in monkeys after lesions of analogous areas and is consistent with the notion that the prefrontal cortical system contributes preferentially to learning general task "rules" such as the nonmatching rule that is inherent in cDNM, whereas the perirhinal and entorhinal cortical areas are involved in the intermediate-term maintenance of memories for specific information.

Animals↗

Learning-related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long-term potentiation.

Recent studies have revealed 3 stimulation parameters that together comprise the temporal pattern of neuronal activation optimal for the induction of hippocampal LTP: high-frequency bursts, activity 100-200 ms prior to a burst, and burst delivery in phase with the ongoing hippocampal theta rhythm. The present paper reports that these 3 aspects of patterned neural activity, collectively referred to as "theta-bursting," are characteristic of the spike trains of CA1 pyramidal cells in rats during the sampling and analysis of learning cues in an odor discrimination task and during performances of a spatial memory task. In contrast, theta-bursting occurs relatively infrequently during behavioral events less directly related to task-relevant mnemonic processing. These findings suggest that the optimal conditions for the induction of LTP occur naturally in behaving animals, time-locked to behavioral events critical to learning.

Animals↗

Hippocampus and olfactory discrimination learning: effects of entorhinal cortex lesions on olfactory learning and memory in a successive-cue, go-no-go task.

Three experiments assessed the effect of entorhinal cortex lesions on olfactory learning and memory using a successive-cue olfactory discrimination paradigm. In contrast to the results of other studies that used a simultaneous-cue paradigm, lesions of the entorhinal cortex facilitated rats' acquisition of individual odor discrimination problems, with no impairment in memory for the individual odors across both short (24-hr) and long (65-day) retention intervals and despite limited training. When considered together with previous observations of facilitation or impairment in learning after damage to the hippocampal system, the present data suggest that the hippocampus is preferentially involved in encoding relations among multiple stimuli. By this account, facilitation of performance is due to an interaction between hippocampal system dysfunction and task conditions that hinder direct comparisons among cues.

Animals↗

Hippocampal representation in place learning.

The generality of the place-learning impairment associated with hippocampal system damage was challenged using methods of training that permitted subjects to form an individual association between the place of escape and a particular navigational route in an open-field water maze. Both normal rats and rats with fornix lesions (FX rats) acquired this task rapidly, although FX rats were slightly slower in achieving minimum escape latencies. In postcriterion testing, FX rats occasionally made near misses but, more often, their escape performance was indistinguishable from that of intact rats. Results from a variety of probe tests indicated that FX rats, like normal rats, had based their performance on a representation of multiple distal cues but their representation, unlike that of normal rats, was inflexible in that it could not be used to guide performance when the cues or starting position were altered. These results parallel those from other studies of hippocampal function in animals and humans: The learning deficit consequent to hippocampal system damage (1) is not specific to a particular category of learning materials, but is dependent on the representational demands of the task; (2) is observed when task demands encourage a representation based on relations among multiple cues, but not when the task encourages adaptation to an individual (or compound) stimulus; (3) spares acquisition of fundamental procedures needed to perform the task; and (4) impairs the flexible use of learned information in tests other than repetition of the learning experience.

Animals↗

Further studies of hippocampal representation during odor discrimination learning.

The contribution of hippocampal and nonhippocampal memory processing to simultaneous-cue odor discrimination learning was assessed. In this task, rats with hippocampal system damage consequent to fornix lesions (fornix rats) were severely and persistently impaired in discrimination learning, acquisition of learning set, and concurrent discrimination, although they occasionally solved some problems at a normal rate. By using those problems on which fornix rats succeeded, to permit comparisons of performance strategies with normal rats, differences between groups were shown on response latency measures and on probe trials involving the novel pairing of familiar odors. Normal rats had a bimodal distribution of response latencies, and their latency depended on where the S+ was presented. Fornix rats had short response latencies and responded equally quickly wherever the S+ was presented. Furthermore, when the representation of familiar S+ and S- odor pairs was challenged in probe trials, normal rats responded appropriately to the correct stimulus, whereas fornix rats behaved as if presented with a new odor pair. These data provide support for the view that the hippocampus participates in the representation of relations among odor (and other) stimuli and among other experiences and that it permits the flexible use of these representations in new contexts. In contrast, memory processing outside the hippocampal system can represent only the significance of individual stimuli and can be revealed only in a repetition of the original learning event.

Animals↗

Spatial and behavioral correlates of hippocampal neuronal activity.

The firing rate of hippocampal neurons in rats was related both to spatial location and to multiple behavioral variables as rats performed 2 kinds of tasks that rely on hippocampal function: a spatial navigation task similar in performance demands to the radial-arm maze task and a simultaneous cue odor-discrimination task. In the place task, most cells had distinct single or multiple place fields, that is, neurons increased firing when the rat was in a particular location or locations. However, in most of these cells, firing rate also varied systematically in relation to behavioral variables, including the speed, direction, and turning angle of the rat as it moved through the place field. In addition, the activity of most cells was time-locked to task-relevant approach movements. In the odor task, most cells fired as the rat sampled discriminative cues or when it executed specific, task-relevant approach movements. Some cells fired selectively in relation to which odors were presented, the configuration of odor cues, the locus of the response, or a combination of these variables. Many cells with spatial correlates in the place task also had striking behavioral correlates when rats performed the odor task in the same environment, and the locus of the increased firing associated with behavior in the odor task was not the same as the place field in the place task. Thus, while the complex stimuli that compose spatial cues are reflected in hippocampal neuronal activity, hippocampal processing is not limited to the representation of spatial location. Rather, the domain of hippocampal representation includes both spatial and nonspatial relations among multiple cues and the actions directed in relation to these cues, across cue modalities, and across behavioral paradigms.

Animals↗

The organization of spatial coding in the hippocampus: a study of neural ensemble activity.

Neural activity was recorded from local groups of hippocampal single units in rats performing a spatial-memory task. The organization of functional correlates in these neural ensembles was investigated by examining the spatial relationships among the place fields of single units in each ensemble. The distance and overlap between place fields were determined together with the tuning of cellular activity to behavioral variables, including direction, speed, and turning angle during movements within place fields. The place fields of recorded neural ensembles were significantly clustered: closer in space and considerably more overlapped than chance when compared statistically with Monte Carlo simulations. Just as single units often have significant firing in more than one distinct location in the environment (subfields), the ensembles had multiple and distinct clusters of overlapping subfields. In addition, proximity and overlap between place fields were significantly, but weakly, correlated with similarity in optimal movement tuning parameters. These results suggest that the hippocampus maintains a local organization with respect to place fields despite having no apparent large-scale isomorphism with the spatial environment. The organization of multiple, clustered place fields with correlated movement tuning properties in small neural ensembles suggests the existence of functional neural ensembles serving to encode multiple sensory and behavioral aspects of a place or event. Such an organization is similar to that observed for neocortical association areas afferent to the hippocampal system.

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