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Howard Eichenbaum

Publications and source records attributed to Howard Eichenbaum.

31 records · Page 2Linked to original sources
PubMed2004

Recollection-like memory retrieval in rats is dependent on the hippocampus.

Recognition memory may be supported by two independent types of retrieval, conscious recollection of a specific experience and a sense of familiarity gained from previous exposure to particular stimuli. In humans, signal detection techniques have been used to distinguish recollection and familiarity, respectively, in asymmetrical and curvilinear components of their receiver operating characteristic (ROC) curves, standard curves that represent item recognition across different levels of confidence or bias. To determine whether animals also employ multiple processes in recognition memory and to explore the anatomical basis of this distinction, we adapted these techniques to examine odour recognition memory in rats. Their ROC curve had asymmetrical and curvilinear components, indicating the existence of both recollection and familiarity in rats. Furthermore, following selective damage to the hippocampus the ROC curve became entirely symmetrical and remained curvilinear, supporting the view that the hippocampus specifically mediates the capacity for recollection.

Animals↗
PubMed2004

The hippocampus and memory for "what," "where," and "when".

Previous studies have indicated that nonhuman animals might have a capacity for episodic-like recall reflected in memory for "what" events that happened "where" and "when". These studies did not identify the brain structures that are critical to this capacity. Here we trained rats to remember single training episodes, each composed of a series of odors presented in different places on an open field. Additional assessments examined the individual contributions of odor and spatial cues to judgments about the order of events. The results indicated that normal rats used a combination of spatial ("where") and olfactory ("what") cues to distinguish "when" events occurred. Rats with lesions of the hippocampus failed in using combinations of spatial and olfactory cues, even as evidence from probe tests and initial sampling behavior indicated spared capacities for perception of spatial and odor cues, as well as some form of memory for those individual cues. These findings indicate that rats integrate "what," "where," and "when" information in memory for single experiences, and that the hippocampus is critical to this capacity.

Animals↗
PubMed2004

Transitive inference in schizophrenia: impairments in relational memory organization.

Transitive inference (TI) describes a fundamental operation of relational (e.g., explicit) memory organization [Eichenbaum, H., Cohen, N.J., 2001. From Conditioning to Conscious Recollection: Memory Systems of the Brain. Oxford Univ. Press]. Here we investigate TI in schizophrenia (SZ), a neurocognitive disorder associated with explicit but not implicit memory dysfunction. SZ patients and healthy controls were trained on a series of learned discriminations that were hierarchically organized (A>B, B>C, C>D, and D>E). They were then tested on each training pair and two novel "inference" pairs: AE, which can be evaluated without consideration of hierarchical relations, and BD, which can only be evaluated by hierarchical relations. SZ patients and controls successfully learned the training pairs and correctly responded to the nonrelational AE pairs. However, SZ patients were less accurate than controls in responding to the relational BD pairs, consistent with the hypothesis that higher-level memory processes associated with relational memory organization are impaired in SZ. The results are discussed with respect to the relational memory model and candidate neuro-cognitive mechanisms of TI.

Adult↗
PubMed2004

Cognitive aging and the hippocampus: how old rats represent new environments.

Spatial learning impairment in aged rats is associated with changes in hippocampal connectivity and plasticity. Several studies have explored the age-related deficit in spatial information processing by recording the location-specific activity of hippocampal neurons (place cells). However, these studies have generated disparate characterizations of place cells in aged rats as unstable (Barnes et al., 1997), resistant to change (Tanila et al., 1997b; Oler and Markus, 2000; Wilson et al., 2003), or delayed in using external cues (Rosenzweig et al., 2003). To reconcile these findings, we recorded place cells from aged and young rats as they repeatedly explored both a highly familiar environment and an initially novel environment, and we repeatedly tested whether the place fields formed in the novel environment were anchored by external cues. Initially, spatial representations in aged rats were abnormally maintained between the familiar and novel environments. Then, new representations were formed but were also delayed in becoming anchored to the external landmarks. Finally, even when the new spatial representations became bound to the landmarks, they were multi-stable across repetitive exposures to the formerly novel environment. These observations help to reconcile previously divergent characterizations of spatial representation in aged rats and suggest a model of cognitive aging and hippocampal function.

Aging↗
PubMed2004

One-trial odor-reward association: a form of event memory not dependent on hippocampal function.

To examine whether the hippocampus is required for memory for unique experiences independent of their spatial or temporal context, the authors devised a novel task that requires rats to remember odor-reward associations formed within a single training trial. Unlike previous tests of 1-trial memory, in this task new associations with otherwise familiar stimuli must be formed, and accurate judgments cannot be based on relative familiarity or recency of the stimuli. The authors show that intact rats performed well on this novel test of event memory. Furthermore, rats with lesions of the hippocampus showed no impairments, even over long retention intervals. These data suggest that the hippocampus is not required for event-specific stimulus-reward associations and that other brain structures mediate this aspect of episodic memory.

Analysis of Variance↗
PubMed2003

Spatial memory performance of freely-moving squirrel monkeys.

Few experiments have addressed the problem of cognitive map formation in non-human primates. Therefore, a paradigm was developed to assess spatial memory formation in squirrel monkeys (Saimiri sciureus) moving freely in three dimensions. While moving on the walls and floor of a large test chamber, the animals learned to collect pieces of cereal from baited food-ports interspersed among non-baited ports. The cereal-pellets were not visible to the monkeys, so the animals needed to develop spatial memory to visit only the baited ports for food and avoid the non-baited ones. A session consisted of ten consecutive trials, and 3 successive sessions were conducted on each day for a 5-day period. For each trial, correct choices (CC; number of visited baited-ports) and incorrect choices (IC; number of visited non-baited ports) were registered, and spatial memory performance index (SMPI; ranging from 0.00 to 1.00) was calculated as follows: SMPI=(CC-IC)/CC. For each session, mean SMPI, session duration, total reaches into the non-baited ports, and total reaches into the baited ports were documented. In an 8-port task, where 4 food-ports were baited and 4 were non-baited, the mean SMPI was higher than 0 in the first session (day 1), indicating the development of short-term spatial memory. By the fifth session (day 2), this index was significantly higher than in the first session, indicating the build-up of long-term spatial memory. These changes were related to a significant decrease in the total reaches into the non-baited ports. At the same time, the duration of the sessions and the total reaches into the baited ports did not change significantly. This paradigm can be used for (1) studying cognitive map formation in primates, (2) examining the underlying cellular and molecular mechanisms in integrative neurobiological experiments, and (3) screening cognition-enhancer drugs in a monkey model.

Analysis of Variance↗
PubMed2003

How does the hippocampus contribute to memory?

Recently, Wirth et al. reported that hippocampal neurons signal the acquisition of new associations by altering the selectivity of their responses to crucial stimuli. The course of these changes was gradual, with some neurons recruited before, others at the time of, and yet others shortly after learning. These observations suggest the hippocampus might contribute to memory by identifying consistencies across experiences that constitute important new associations.

Journal Article↗
PubMed2002

The hippocampus and disambiguation of overlapping sequences.

Recent models of hippocampal function emphasize its potential role in disambiguating sequences of events that compose distinct episodic memories. In this study, rats were trained to distinguish two overlapping sequences of odor choices. The capacity to disambiguate the sequences was measured by the critical odor choice after the overlapping elements of the sequences. When the sequences were presented in rapid alternation, damage to the hippocampus, produced either by infusions of the neurotoxin ibotenic acid or by radiofrequency current, produced a severe deficit, although animals with radiofrequency lesions relearned the task. When the sequences were presented spaced apart and in random order, animals with radiofrequency hippocampal lesions could perform the task. However, they failed when a memory delay was imposed before the critical choice. These findings support the hypothesis that the hippocampus is involved in representing sequences of nonspatial events, particularly when interference between the sequences is high or when animals must remember across a substantial delay preceding items in a current sequence.

Animals↗
PubMed2002

Cholinergic system regulation of spatial representation by the hippocampus.

The role of the basal forebrain cholinergic system in hippocampal spatial representation was explored by examining the effects of immunotoxic lesions of the septo-hippocampal cholinergic neurons on the firing patterns of hippocampal place cells as rats explored familiar and novel environments. In a highly familiar environment, the basic qualities and stability of place fields were unaffected by the lesion. When first exposed to a set of novel environmental cues without otherwise disorienting the animals, place cells in both normal and lesioned animals responded with similar alterations in their firing patterns. Upon subsequent repetitive exposures to the new environment, place cells of normal rats developed a spatial representation distinct from that of the familiar environment. By contrast, place cells of lesioned animals reconverged in the direction of the representation associated with the familiar environment. These results suggest that cholinergic input may determine whether new visual information or a stored representation of the current environment will be actively processed in the hippocampal network.

Animals↗
PubMed2002

Hippocampal formation lesions impair performance in an odor-odor association task independently of spatial context.

The rodent hippocampal system is known to play an important role in memory. Evidence that this role is not limited to spatial memory has come from studies using a variety of non-spatial memory tasks. One example is the social transmission of food preference paradigm, a task in which rats learn an odor-odor association with no explicit spatial memory component. However, because training and testing in this task typically take place in the same environment, it is possible that memory for the spatial context in which odors are experienced during training is critical to subsequent retention performance. If this is the case, it might be expected that lesions of the hippocampal system would impair memory performance by disrupting the establishment of a representation of the training environment. We addressed this issue by training rats in one spatial context and then testing them either in the same or a different spatial context. Normal control rats performed equally well when tested in an environment that was the same or different from that used during training, and the retention impairment exhibited by rats with hippocampus plus subiculum lesions was equivalent in the two test environments. These results support the view that the hippocampal system is necessary for the flexible expression of nonspatial memories even when the spatial context in which the memory is acquired is not critical to retrieval.

Animals↗
PubMed2002

Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats.

We examined the performance of Long-Evans rats with 192 IgG-saporin lesions of the medial septum/vertical limb of the diagonal band (MS/VDB) or nucleus basalis magnocellularis/substantia innominata (NBM/SI), which removed cholinergic projections mainly to hippocampus or neocortex, respectively. We studied the effects of these lesions on anterograde and retrograde memory for a natural form of hippocampal-dependent associative memory, the social transmission of food preference. In a study of anterograde memory, MS/VDB lesions did not affect the immediate, 24-h or 3-week retention of the task. In contrast, NBM/SI lesions severely impaired immediate and 24-h retention. In a study of retrograde memory in which rats acquired the food preference 5 days or 1 day before surgery and they were tested 10-11 days after surgery, MS/VDB-lesioned rats showed striking memory deficits for the preference acquired at a long delay (5 days) before surgery, although all lesioned rats exhibited poorer retention on both retest sessions than on their pretest performance. Subsequent testing of new anterograde learning in these rats revealed no disrupting effects of lesions on a standard two-choice test. When rats were administered a three-choice test, in which the target food was presented along with two more options, NBM/SI-lesioned rats were somewhat impaired on a 24-h retention test. These results provide evidence that NBM/SI and MS/VDB cholinergic neurons are differentially involved in a social memory task that uses olfactory cues, suggesting a role for these neurons in acquisition and consolidation/retrieval of nonspatial declarative memory.

Amnesia, Anterograde↗
PubMed2002

Representations of odors in the rat orbitofrontal cortex change during and after learning.

Cells in the orbitofrontal cortex (OF) respond to odors and their associated rewards. To determine how these responses are acquired and maintained, the authors recorded single OF units in rats performing an odor discrimination task. Approximately 64% of all cells differentiated between rewarded and nonrewarded odors. These odor valence responses changed during learning in 26% of all cells, and these changes were positively correlated with improving performance, supporting the idea that the information provided by these cells is used in learning the task. However, changes in odor valence responses were also observed after learning, and included not only increases in odor discrimination, but also decreases or mixed increases and decreases. Thus, only some of the changes in firing reflected acquisition of the task. The results suggest that learning triggers a continuing reorganization of OF neural ensembles representing odors and their rewards.

Action Potentials↗