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Biomedical subjects

H Eichenbaum

Publications and source records attributed to H Eichenbaum.

At least 73 records · Page 4Linked to original sources

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.

Animals↗

Hippocampal system dysfunction and odor discrimination learning in rats: impairment or facilitation depending on representational demands.

The performance of normal rats and that of rats with hippocampal system damage were compared on acquisition of different versions of the same two-odor discrimination task that placed different encoding and representational demands on memory. Rats with fornix lesions were impaired when explicit comparisons among multiple odor cues and differential response choices were encouraged. However, when odor-cue comparison was hindered and explicit cues for response choice were eliminated, rats with fornix lesions out performed normal animals. The results support an hypothesis that the hippocampal system is critical to a memory representation based on encoding relations among multiple percepts, and other brain systems support performance adaptations based on encodings of stimuli individually.

Animals↗

Cue-sampling and goal-approach correlates of hippocampal unit activity in rats performing an odor-discrimination task.

Several techniques previously used to describe behavioral correlates of hippocampal unit and slow-wave activity are combined in a single odor-discrimination paradigm. Rats repetitively performed a sequence of behaviors during each trial: approach to a stimulus-sampling port, investigatory sniffing of the odor cue, orientation and approach toward a separate reward location, and water reward consumption. In a series of post hoc analyses, spike activity was time-locked to variations of each task event to uncover behavioral and physiological parameters that best synchronized unit firing. Three major categories of cells were identified: (1) "Cue-sampling" cells fired after onset of odor-cue sampling. Response magnitude was related to cue valence on both the current and past trials. (2) "Goal-approach" cells fired prior to arrival at either the odor-sampling port or reward cup. A number of sampling and approach cells also had place correlates. However, detailed analyses indicated that specific behaviors associated with increased firing reliably occurred at the same place. Unit activity was at least as well described by behavioral as spatial parameters. (3) "Theta" cells fired at high rates in strict relation to the ongoing limbic theta rhythm. This categorization suggests a functional organization of the hippocampus in which different cell types play complementary roles. Cue-sampling cells activated by discriminative stimuli during attentive fixations may be involved in comparing relative cue valence. Goal-approach cells may be involved in orientation movements for successive cue-sampling periods. Theta cells may provide synchronization of sensory acquisition during sampling, as well as in orientation movements during approach.

Animals↗

Neural group properties in the rat hippocampus during the theta rhythm.

The ensemble properties of unit activity in the rat hippocampus were studied during different behavioral states defined by the presence or absence of the theta rhythm. A 24-channel microelectrode was used to monitor the parallel activity of several single neurons simultaneously. Individual units were characterized by waveform, firing repertoire and firing relation to theta phase. Group patterns were characterized by multiple cross-correlations at different temporal resolutions during the presence and absence of the theta rhythm. Coactivation of units was frequently observed at a fine temporal resolution under both theta and non-theta states. In addition rhythmic synchronization of units was observed at a broader temporal resolution and was selective to the theta state. The combined findings suggest that the theta rhythm signifies a powerful patterning of group activity imposed upon a fixed connectivity of neighboring neurons.

Animals↗

Normal olfactory discrimination learning set and facilitation of reversal learning after medial-temporal damage in rats: implications for an account of preserved learning abilities in amnesia.

Recent evidence of preserved skill learning in patients with "global" amnesia has led to the postulation of a qualitative distinction between functionally separate memory systems, one of which may remain preserved when the other is profoundly impaired. On one account, the separate memory systems support either the learning of declarative knowledge, i.e., facts and associations, or the learning of procedural knowledge, i.e., knowledge that permits the expression of skilled performance without reference to specific facts or associations. In an effort to develop a rodent model of amnesia that illustrates the same distinction between memory systems, rats were trained in a series of discrimination and reversal problems using olfaction, a sensory modality in which they rapidly learn new associations. Rats with bilateral fornix, amygdala, or combined fornix and amygdala damage learned successive two-odor discriminations as quickly as normal and sham-operated control subjects. Furthermore, all groups rapidly acquired the skills of discrimination as revealed in the development of a learning set. Subsequent presentation of a reversal of one discrimination elicited a marked dissociation among groups: Normal rats and rats with amygdala lesions required many more trials to acquire the reversal than to acquire a new discrimination problem, whereas rats with fornix lesions learned the reversal rather easily. A detailed analysis of response strategies suggested that normal rats and rats with amygdala lesions first extinguished the prior response tendencies and then abandoned the learning set skills and treated the reversal much as they did the initial discrimination problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Amnesia↗

Unit activity, evoked potentials and slow waves in the rat hippocampus and olfactory bulb recorded with a 24-channel microelectrode.

Activity from a number of neighboring neurons can be recorded simultaneously with multichannel microelectrodes. A new version of a 24-channel microelectrode system has been fabricated and used to record different types of neurophysiological data in the rat brain. The system called PRONG (Parallel Recording Of Neural Groups) includes a microelectrode, a lightweight reusable connector, a 24-channel FET-hybrid preamplifier, a 3-band 24-channel amplifier, a 24-channel spike monitor, high-speed digital and analog interfaces and a computer. The electrode-recording locations are arranged in 2 arrays of 12 sites. The arrays are spaced 100 micron apart along either edge of the recording section and the sites within each array are spaced 120 micron apart. The electrodes are fabricated using photolithography in patterned layers totaling 17 micron thick and 114 micron wide in the recording section. The recording sites are 20 micron2 and are plated with platinum black. Performance of the PRONG was compared with that of conventional single microelectrodes and with results in the literature on three kinds of extracellular activity in the rat hippocampal formation and olfactory bulb: action potentials, evoked field potentials and slow-wave activity. The selectivity and sensitivity of the PRONG compared favorably with characteristics of conventional electrodes. Background noise averaged 15 microV and no signal cross talk was observed between neighboring channels. Discriminable action potentials (signal-to-noise ratios of 2:1 to 15:1) were observed at 37-95% of the viable recording sites with a maximum of 19 units in one recording. Units were observed in waking animals for up to 4 days. The waveforms, firing repertoires and laminar distribution of units were the same as those recorded with conventional microelectrodes. This indicates that penetration by the PRONG spares tissue from functional damage. "Instant" laminar profiles were created for commissural and perforant path evoked potentials in the hippocampal formation. These profiles were nearly identical with those created by successive recordings made with conventional microelectrodes. Laminar profiles and behavioral activity appeared to be "normal" as collected with this electrode. These results set the foundation for use of the PRONG as a tool for the study of local neural interactions.

Animals↗

Diminished ability to interpret and report internal states after bilateral medial temporal resection: case H.M.

These experiments centered around H.M., a 54-year-old man who became amnesic 27 years ago after a bilateral resection in the medial temporal lobe region for epilepsy. In order to document the clinical reports that he rarely comments on such internal states as pain, hunger, and thirst, his thermal pain perception was examined in relation to his other somatosensory capacities, and his reports of hunger and thirst were assessed before and after meals. In order to investigate the effect of limited memory ability on the reporting of internal states, H.M.'s performance was compared with that of 5 other subjects with global amnesia. The results provided evidence that H.M.'s information about internal states is less available or less accessible than normal and that his impairment is not attributable to his well-documented memory deficit. Instead, it is believed that the bilateral resection of the amygdala accounts for H.M.'s poor appreciation of his internal states.

Adult↗

Afferent connections of the perirhinal cortex in the rat.

Connections of the perirhinal cortex in the rat brain were studied using anterograde (3H-proline/leucine) and retrograde (horseradish peroxidase) tracers. The perirhinal cortex receives major projections from medial precentral, anterior cingulate, prelimbic, ventral lateral orbital, ventral and posterior agranular insular, temporal, superior and granular parietal, lateral occipital, agranular retrosplenial, and ectorhinal cortices, and from the presubiculum, subiculum, and diagonal band of Broca. Rostral neocortical areas project predominantly to rostral perirhinal regions while more caudal neocortical and subicular areas project predominantly to caudal perirhinal regions. Terminal fields are further segregated within perirhinal cortex to either the dorsal or ventral banks of the rhinal sulcus. All afferents from frontal areas terminate predominantly in the deep layers of its ventral bank; afferents from temporal, parietal, and lateral occipital areas terminate predominantly in the deep and superficial layers along its dorsal bank; and afferents from ectorhinal cortex terminate in a column within its dorsal bank. Cortical cells which project to perirhinal areas are found predominantly in layer II and the superficial part of layer III. However, ventrolateral orbital, parietal, and lateral occipital cortex projections originate predominantly from layer V. Perirhinal areas also receive afferents from the nucleus reuniens of the thalamus, lateral nucleus of the amygdala, claustrum, supramammillary nuclei, and the dorsal raphe nuclei.

Afferent Pathways↗

Reexamination of functional subdivisions of the rodent prefrontal cortex.

Selective patterns of behavioral deficits were observed on tests of spatial or olfactory learning after different cortical lesions in rats. The results clearly distinguished functional subdivisions of the rodent prefrontal cortex: Rats with lesions of the prefrontal cortex that primarily involve the dorsal bank of the rhinal sulcus were impaired selectively and exhibited increased perseveration of responses in a go, no-go odor discrimination task. In contrast, rats with lesions of the region of prefrontal cortex situated along the medial cortical wall were impaired selectively and exhibited increased perseveration of responses in a spatial delayed alteration task. These behavioral deficits were similar in magnitude and quality to those found in monkeys after discrete ablations of frontal lobe regions that are argued to be homologous prefrontal subdivisions.

Animals↗

Selective olfactory deficits in case H.M.

A variety of olfactory capacities were evaluated in H.M., a patient with bilateral medial temporal lobe resection. He demonstrated normal performance on a battery of tests of odour detection, discrimination of intensity, and adaptation. In striking contrast, H.M. was unable to discriminate or identify odours in same-different discriminations and in matching-to-sample tasks. Although he could name common objects using visual or tactile cues, he could not identify them by smell. These results indicate that the perceptual phenomena of odour detection and discrimination are dissociable by cerebral damage, and that structures in the medial temporal lobe play a critical role in odour discrimination.

Brain Diseases↗

The role of frontal cortex-reticular interactions in performance and extinction of the classically conditioned nictitating membrane response in the rabbit.

In order to investigate the behavioral role of interactions between frontal cortex and reticular nuclei, we examined the effects of single and combined lesions of these structures on the classically conditioned nictitating membrane response (NMR) of rabbits. Lesions of frontal cortex decreased latencies of the conditioned NMRs in reacquisition and retarded extinction of the conditioned response. Lesions of nucleus reticularis pontis oralis (NRPO) produced similar effects. In contrast, lesions of nucleus reticularis tegmenti (NRT) increased NMR latencies during reacquisition. The opposite effects of frontal cortex and NRT lesions were abolished when the two lesions were combined, indicating that the two lesion effects summed. In contrast, the deficits due to frontal and NRPO lesions did not sum; combined frontal-NRPO lesions produced deficits very similar in magnitude and time course to those of the NRPO lesions alone. These findings suggest that frontal cortex may exert its inhibitory effects on behavior not by directly interacting with NRT, but by facilitating NRPO, which in turn may inhibit the nucleus of the VIth nerve, the final common pathway to the NMR. NRT may facilitate the motor pathway by modulating the inhibitory effect of NRPO on the VIth nerve nucleus.

Animals↗

Thalamocortical mechanisms in odor-guided behavior. I. Effects of lesions of the mediodorsal thalamic nucleus and frontal cortex on olfactory discrimination in the rat.

The "core" subnucleus of the mediodorsal thalamic nucleus (MD) receives direct input from olfactory cortex in the rat. This part of MD projects to the frontal neocortex of the rhinal sulcus (RS), while other parts of the MD project to the anterior medial wall of the neocortex (MW). In this study, rats were tested on odor threshold, detection of specific odors, and three odor discriminations both before and after lesions of MD, MW, RS, or sham lesions. Olfactory threshold and detection ability remained unaffected by any of these lesions; however, subjects with MD and RS lesions were markedly impaired on odor discriminations. Furthermore, subjects were more profoundly impaired when the stimuli to be discriminated were novel or difficult to associate. Thus, MD and its "olfactory" projection target, RS, seem to mediate cognitive, rather than sensory aspects of odor-guided behavior in the rat.

Animals↗

Thalamocortical mechanisms in odor-guided behavior. II. Effects of lesions of the mediodorsal thalamic nucleus and frontal cortex on odor preferences and sexual behavior in the hamster.

The role of the thalamocortical "olfactory" pathway in odor preferences and sexual behavior was examined in the hamster, a species which depends crucially upon olfaction for mating. Before and after ablation of primary or secondary olfactory structures, male hamsters were tested for threshold, interest, and preference for the odor of an estrus female hamster and other odors. Sexual competency was also observed in daily mating sessions. Disruption of the primary olfactory pathway resulted in an absence of interest in odors and mating. Lesions of the mediodorsal thalamic nucleus or frontal neocortex of the rhinal sulcus did not result in anosmia, but did eliminate or alter odor preferences and resulted in inappropriate, inefficient, precopulatory and copulatory behavior. It appears that substructures in the thalamofrontal pathway playa role in discriminative or cognitive aspects of processing adaptively significant stimuli.

Animals↗