Biomedical subjects

Howard Eichenbaum

Publications and source records attributed to Howard Eichenbaum.

At least 19 recordsLinked to original sources

PubMed2006

Neurocognitive aging: prior memories hinder new hippocampal encoding.

Normal aging is often accompanied by impairments in forming new memories, and studies of aging rodents have revealed structural and functional changes to the hippocampus that might point to the mechanisms behind such memory loss. In this article, we synthesize recent neurobiological and neurophysiological findings into a model of the information-processing circuit of the aging hippocampus. The key point of the model is that small concurrent changes during aging strengthen the auto-associative network of the CA3 subregion at the cost of processing new information coming in from the entorhinal cortex. As a result of such reorganization in aged memory-impaired individuals, information that is already stored would become the dominant pattern of the hippocampus to the detriment of the ability to encode new information.

Aging↗

PubMed2006

Gradual translocation of spatial correlates of neuronal firing in the hippocampus toward prospective reward locations.

In a continuous T-maze alternation task, CA1 complex-spike neurons in the hippocampus differentially fire as the rat traverses overlapping segments of the maze (i.e., the stem) repeatedly via alternate routes. The temporal dynamics of this phenomenon were further investigated in the current study. Rats learned the alternation task from the first day of acquisition and the differential firing pattern in the stem was observed accordingly. More importantly, we report a phenomenon in which spatial correlates of CA1 neuronal ensembles gradually changed from their original firing locations, shifting toward prospective goal locations in the continuous T-maze alternation task. The relative locations of simultaneously recorded firing fields, however, were preserved within the ensemble spatial representation during this shifting. The within-session shifts in preferred firing locations in the absence of any changes in the environment suggest that certain cognitive factors can significantly alter the location-bound coding scheme of hippocampal neurons.

Animals↗

PubMed2006

Remembering: functional organization of the declarative memory system.

How do brain systems support our subjective experience of recollection and our senses of familiarity and novelty? A new functional imaging study concludes that each of these functions is accomplished by a distinct component of the medial temporal lobe, shedding new light on the functional organization of this memory system.

Hippocampus↗

PubMed2006

Hippocampal CA1 spiking during encoding and retrieval: relation to theta phase.

The hippocampal theta rhythm is a prominent oscillation in the field potential observed throughout the hippocampus as a rat investigates stimuli in the environment. A recent computational model [Hasselmo, M. E., Bodelon, C., & Wyble, B. P. (2002a). A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Computation, 14, 793-817. Neuromodulation, theta rhythm and rat spatial navigation. Neural Networks, 15, 689-707] suggested that the theta rhythm allows the hippocampal formation to alternate rapidly between conditions that promote memory encoding (strong synaptic input from entorhinal cortex to areas CA3 and CA1) and conditions that promote memory retrieval (strong synaptic input from CA3 to CA1). That model predicted that the preferred theta phase of CA1 spiking should differ for information being encoded versus information being retrieved. In the present study, the spiking activity of CA1 pyramidal cells was recorded while rats performed either an odor-cued delayed nonmatch-to-sample recognition memory test or an object recognition memory task based on the animal's spontaneous preference for novelty. In the test period of both tasks, the preferred theta phase exhibited by CA1 pyramidal cells differed between moments when the rat inspected repeated (match) and non-repeated (nonmatch) items. Also in the present study, additional modeling work extended the previous model to address the mean phase of CA1 spiking associated with stimuli inducing varying levels of retrieval relative to encoding, ranging from novel nonmatch stimuli with no retrieval to highly familiar repeated stimuli with extensive retrieval. The modeling results obtained here demonstrated that the experimentally observed phase differences are consistent with different levels of CA3 synaptic input to CA1 during recognition of repeated items.

Animals↗

PubMed2006

The secret life of memories.

Recent evidence has challenged the view that memories are made permanent by a consolidation process that happens just once and instead have suggested that memories are "re-consolidated" after reminders. The current findings of Morris et al. in this issue of Neuron suggest that reconsolidation may involve a complex interaction between synaptic and system processing of recent as well as remote experiences.

Animals↗

PubMed2006

Dynamics of hippocampal and cortical activation during consolidation of a nonspatial memory.

Observations of temporally graded retrograde amnesia after hippocampal damage suggest that the hippocampal region plays a critical, time-limited role in memory consolidation. However, these observations do not indicate where permanent memory is stored, nor do they clarify whether the hippocampus normally remains involved in a nonessential way. Evidence from multiple neural imaging studies indicate the time-limited role of the hippocampus and suggest that the anterior cingulate cortex is a critical storage site of different types of long-term memory. However, each of the previous studies examined spatial memory, leaving open the question of whether different cortical areas support long-term memory for other types of material. We characterized the course of involvement of cortical and hippocampal areas in animals trained in an explicitly nonspatial task. First, we confirmed previous findings that hippocampal damage produces temporally graded retrograde amnesia for the social transmission of a food preference (STFP) within our experimental protocol. Damage to the hippocampal region 1 d, but not 21 d, after training impaired subsequent recall of STFP. Then, we characterized the anatomical patterns of activation of the immediate early gene c-fos during retrieval of STFP immediately and 1, 2, and 21 d after training. The ventral subiculum was activated during retrieval shortly after learning, but the level of activation declined at successive times. In contrast, olfactory recipient regions including piriform, entorhinal, and orbitofrontal cortex showed the opposite pattern, increasingly greater activation in successively later retrieval tests. These findings support the view that different cortical networks support long-term memory for different types of information.

Analysis of Variance↗

PubMed2006

Essential role of the hippocampal formation in rapid learning of higher-order sequential associations.

Evidence from studies of amnesia and functional imaging in humans suggest that the medial temporal lobe is involved in the learning of higher-order sequences during acquisition of serial reaction time (SRT) tasks. However, these studies have not clarified whether the hippocampal formation specifically is essential to this type of learning. Here, we developed a rodent model of the SRT task to examine the specific roles of the hippocampal formation in learning first- and second-order conditional sequences. Selective hippocampal formation lesions speeded performance and impaired accuracy on both first- and second-order sequences. Additionally, whereas controls distinguished the sequences based on their complexity alone, animals with hippocampal lesions initially differentiated sequences only by their length. Over multiple sessions, hippocampal rats gradually differentiated sequences by their complexity and not length, similar to control subjects. These findings indicate that the hippocampal formation itself plays an essential role in rapid acquisition of higher-order sequence representations. Extrahippocampal systems can also acquire complex sequential representations, albeit via a gradual learning mechanism.

Animals↗

PubMed2006

The role of CA3 hippocampal NMDA receptors in paired associate learning.

The hippocampus is necessary for declarative memory in humans and episodic memory in rodents. Considerable current research is focused on the role of plasticity within specific subfields of the hippocampus. Here, using a viral vector to temporally control a focal deletion of the NR1 gene, we show that learning novel paired associations between specific cues and their context is dependent on CA3 NMDA receptors. Deletion of CA3 NR1 genes in <30% of the dorsal hippocampus was sufficient to disrupt new learning, whereas the same treatment does not prevent expression of previously acquired paired associates and does not affect the ability to discriminate contexts or paired associate learning when either the cues or the context is familiar. The findings suggest that CA3 NMDA receptors specifically support the encoding of new experiences to involve incidental and contingent associations.

Animals↗

PubMed2006

Evolution of declarative memory.

The present review considers research on the hippocampus and related areas from humans and experimental animals and makes three main points. First, many of the anatomical details of the hippocampus and adjacent cortical areas in the parahippocampal region are conserved across mammals. Second, the functional role of these areas in declarative memory is also conserved across species. Third, an evolutionary approach will be key to understanding exactly how the local circuitry of the hippocampus and parahippocampal region supports declarative memory. To highlight the utility of this approach, a schematic model is described in which separate streams of spatial and nonspatial information converge on the hippocampus. By this view, a fundamental function of the mammalian hippocampus is to combine incoming information about spatial context from the postrhinal (parahippocampal in primates) cortex and medial entorhinal area with incoming information about nonspatial items from the perirhinal cortex and lateral entorhinal area. The underlying neurobiological computations that arise from local circuitry enable item-in-context memory and are proposed to be fundamental to many examples of declarative memory, including episodic memory in humans and spatial memory in experimental animals.

Animals↗

PubMed2005

Hippocampal mechanisms for the context-dependent retrieval of episodes.

Behaviors ranging from delivering newspapers to waiting tables depend on remembering previous episodes to avoid incorrect repetition. Physiologically, this requires mechanisms for long-term storage and selective retrieval of episodes based on the time of occurrence, despite variable intervals and similarity of events in a familiar environment. Here, this process has been modeled based on the physiological properties of the hippocampal formation, including mechanisms for sustained activity in entorhinal cortex and theta rhythm oscillations in hippocampal subregions. The model simulates the context-sensitive firing properties of hippocampal neurons including trial-specific firing during spatial alternation and trial by trial changes in theta phase precession on a linear track. This activity is used to guide behavior, and lesions of the hippocampal network impair memory-guided behavior. The model links data at the cellular level to behavior at the systems level, describing a physiologically plausible mechanism for the brain to recall a given episode which occurred at a specific place and time.

Animals↗

PubMed2005

Cholinergic deafferentation of the entorhinal cortex in rats impairs encoding of novel but not familiar stimuli in a delayed nonmatch-to-sample task.

Acetylcholine may regulate working memory for novel stimuli by activating intrinsic mechanisms for sustained spiking in entorhinal cortical neurons, which have been demonstrated in slice preparations of the entorhinal cortex. Computational modeling demonstrates that loss of the cholinergic activation of intrinsic mechanisms for sustained activity could selectively impair working memory for novel stimuli, whereas working memory for familiar stimuli could be maintained because of previously modified synapses. Blockade of muscarinic cholinergic receptors and selective cholinergic lesions has been shown to impair encoding in delayed matching tasks. However, previous studies have not compared explicitly the role of cholinergic modulation in working memory for novel versus familiar stimuli. Here, we show that lesions of the cholinergic innervation of the entorhinal cortex selectively impair delayed nonmatch to sample performance for novel odors, whereas delayed nonmatch to sample for familiar odors is spared. This indicates an important role for cholinergic innervation of the entorhinal cortex in working memory for novel stimuli.

Afferent Pathways↗

PubMed2005

Age-associated alterations of hippocampal place cells are subregion specific.

Aging is associated with spatial memory impairments and with deficient encoding of information by the hippocampus. In young adult rats, recent studies on the firing properties of hippocampal neurons have emphasized the importance of the CA3 subregion in the rapid encoding of new spatial information. Here, we compared the spatial firing patterns of CA1 and CA3 neurons in aged memory-impaired rats with those of young rats as they explored familiar and novel environments. We found that CA1 place cells in aged and young rats had similar firing characteristics in the familiar and novel environments. In contrast, aged CA3 place cells had higher firing rates in general and failed to change their firing rates and place fields as much as CA3 cells of young rats when the rats were introduced to a novel environment. Thus, aged CA3 cells failed to rapidly encode new spatial information compared with young CA3 cells. These data suggest an important and selective contribution of CA3 dysfunction to age-related memory impairment.

Action Potentials↗

PubMed2005

Acetylcholine in the orbitofrontal cortex is necessary for the acquisition of a socially transmitted food preference.

The social transmission of food preference task (STFP) has been used to examine the involvement of the hippocampus in learning and memory for a natural odor-odor association. However, cortical involvement in STFP has not been extensively studied. The orbitofrontal cortex (OFC) is important in odor-guided learning, and cholinergic depletion of the entire neocortex results in impairments in STFP. Here we examined the specific role of cholinergic modulation in the OFC by assessing the effect of 192 immunoglobulin G-saporin infusion directly into OFC prior to training on STFP. Cholinergic depletion in the OFC impaired expression of the socially transmitted odor association measured 2 d after training, indicating that cholinergic function in the OFC is essential for this form of associative learning.

Acetylcholine↗

PubMed2005

Time and treason to the trisynaptic teachings: theoretical comment on Kesner et Al. (2005).

Early descriptions of the hippocampal formation emphasized the serial nature of its circuitry, a description that suggests even a focal lesion would break a chain of processing and leave the entire region inoperative. Nevertheless, R. P. Kesner, M. R. Hunsaker, and P. E. Gilbert (2005) show that rats with CA1 lesions, but not rats with CA3 lesions, were impaired on a task in which animals were required to make associations between an object and an odor that were separated by a brief (10-s) delay. The present commentary makes 2 points relevant to their findings. First, several lines of evidence suggest that CA1 can operate somewhat independently of CA3 in some instances. Second, it is unclear whether the delay interval acted directly (by requiring a memory for a timeline of events) or indirectly (by outlasting the associative abilities of areas other than CA1) in causing performance to depend on the integrity of CA1.

Animals↗

PubMed2005

Bridging the gap between brain and behavior: cognitive and neural mechanisms of episodic memory.

The notion that non-human animals are capable of episodic memory is highly controversial. Here, we review recent behavioral work from our laboratory showing that the fundamental features of episodic memory can be observed in rats and that, as in humans, this capacity relies on the hippocampus. We also discuss electrophysiological evidence, from our laboratory and that of others, pointing to associative and sequential coding in hippocampal cells as potential neural mechanisms underlying episodic memory.

Animals↗

PubMed2004

Place cells of aged rats in two visually identical compartments.

Aged rats perform poorly on spatial learning tasks, a cognitive impairment which has been linked to the failure of hippocampal networks to fully encode changes in the external environment [Barnes CA, Suster MS, Shen J, McNaughton BL. Multistability of cognitive maps in the hippocampus of old rats. Nature 1997;388(6639):272-5; Wilson IA, Ikonen S, Gureviciene I, McMahan RW, Gallagher M, Eichenbaum H, et al. Cognitive aging and the hippocampus: how old rats represent new environments. J Neurosci 2004;24(15):3870-8]. To examine whether the impairment in hippocampal processing extends to conditions in which self-motion provides the cues for environmental change, we have analyzed spatial firing patterns of hippocampal pyramidal neurons in young and aged rats, as well as in young rats with selective cholinergic lesions, another model of cognitive aging. The rats walked between two visually identical environments, pitting self-motion cues that indicated environmental change against visual inputs that indicated no differences between environments. Our results indicated that place cells in both aged and cholinergic-lesioned rats were equally likely as those of young rats to create new spatial representations in the second compartment. These findings suggest that the hippocampal network of aged rats is able to process changes in internally generated cues without rigidity, but that incomplete processing of external landmark cues may lead to impaired spatial learning.

Action Potentials↗

PubMed2004

Entorhinal cortex lesions disrupt the relational organization of memory in monkeys.

Recent accounts suggest that the hippocampal system critically supports two central characteristics of episodic memory: the ability to establish and maintain representations for the salient relationships between experienced events (relational representation) and the capacity to flexibly manipulate memory (flexible memory expression). To test this proposal in monkeys, intact controls and subjects with bilateral aspiration lesions of the entorhinal cortex were trained postoperatively on two standard memory tasks, delayed nonmatchingto-sample (DNMS) and two-choice object discrimination (OD) learning, and three procedures intended to emphasize relational representation and flexible memory expression: a paired associate (PA) task, a transitive inference (TI) test of learning and memory for hierarchical stimulus relationships, and a spatial delayed recognition span (SDRS) procedure. The latter assessments each included critical "probe" tests that asked monkeys to evaluate the relationships among previously learned stimuli presented in novel combinations. Subjects with entorhinal cortex lesions scored as accurately as controls on all phases of DNMS and OD, procedures that can be solved on the basis of memory for individual stimuli. In contrast, experimental monkeys displayed deficits relative to controls on all phases of the PA, TI, and SDRS tasks that emphasized the flexible manipulation of memory for the relationships between familiar items. Together, the findings support the conclusion that the primate hippocampal system critically enables the relational organization of declarative memory.

Animals↗

PubMed2004

Hippocampus: cognitive processes and neural representations that underlie declarative memory.

The hippocampus serves a critical role in declarative memory--our capacity to recall everyday facts and events. Recent studies using functional brain imaging in humans and neuropsychological analyses of humans and animals with hippocampal damage have revealed some of the elemental cognitive processes mediated by the hippocampus. In addition, recent characterizations of neuronal firing patterns in behaving animals and humans have suggested how neural representations in the hippocampus underlie those elemental cognitive processes in the service of declarative memory.

Animals↗