Hippocampal Unit Activity Research Articles

Altered hippocampal information coding and network synchrony in APP-PS1 mice

β-amyloid is hypothesized to harm neural function and cognitive abilities by perturbing synaptic transmission and plasticity in Alzheimer's disease (AD). To assess the impact of this pathology on hippocampal neurons' ability to encode flexibly environmental information across learning, we performed electrophysiological recordings of CA1 hippocampal unit activity in AD transgenic mice as they acquired an action-reward association in a spatially defined environment; the behavioral task enabled the precise timing of discrete and intentional behaviors of the animal. We found that the proportion of behavioral task-sensitive cells in wild-type (WT) mice typically increased, whereas the proportion of place cells decreased with learning. In AD mice, this learning-dependent change of cell-discharge patterns was absent, and cells exhibited similar firings from the beginning to firings attained at the late learning stage in wild-type cells. These inflexible hippocampal representations of task and space throughout learning are accompanied by remarkable alterations of local oscillatory activity in the theta and ultra-fast ripple frequencies as well as learning abilities. The present data offer new insights into the in vivo cellular and network processes by which β-amyloid and other AD mutations may exert its harmful effects to produce cognitive and behavioral impairments in early stage of AD.

Neocortical Activation of the Hippocampus during Sleep in Infant Rats

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5- to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.

Trial Outcome and Associative Learning Signals in the Monkey Hippocampus

In tasks of associative learning, animals establish new links between unrelated items by using information about trial outcome to strengthen correct/rewarded associations and modify incorrect/unrewarded ones. To study how hippocampal neurons convey information about reward and trial outcome during new associative learning, we recorded hippocampal neurons as monkeys learned novel object-place associations. A large population of hippocampal neurons (50%) signaled trial outcome by differentiating between correct and error trials during the period after the behavioral response. About half these cells increased their activity following correct trials (correct up cells) while the remaining half fired more following error trials (error up cells). Moreover, correct up cells, but not error up cells, conveyed information about learning by increasing their stimulus-selective response properties with behavioral learning. These findings suggest that information about successful trial outcome conveyed by correct up cells may influence new associative learning through changes in the cell's stimulus-selective response properties.

Dehydroepiandrosterone sulfate and estrone sulfate reduce GABA‐recurrent inhibition in the hippocampus via muscarinic acetylcholine receptors

Several recent studies have established a role for estrogens in ameliorating specific neurodegenerative disorders, mainly those associated with the cholinergic neurons of the basal forebrain and their targets in the cortex and hippocampus. We have previously demonstrated that endogenous and exogenous application of the neurosteroid dehydroepiandrosterone sulfate (DHEAS) markedly reduces GABA-mediated recurrent inhibition and synchronizes hippocampal unit activity to theta rhythm (Steffensen (1995) Hippocampus 5:320-328). In this study, we evaluated the role of muscarinic receptors in mediating the effects of DHEAS and estrone sulfate (ES), the principal circulating estrogen in humans, on short-latency-evoked potential responses, paired-pulse inhibition (PPI), paired-pulse facilitation, and GABA interneuron activity in the dentate gyrus and CA1 subfields of the rat hippocampus. In situ microelectrophoretic application of the muscarinic M2 subtype cholinergic receptor agonist cis-dioxolane, DHEAS, and ES markedly reduced PPI in the dentate and CA1 that was blocked by the M2 receptor antagonist gallamine. Similar to DHEAS, microelectrophoretic administration of ES increased population spike amplitudes, without increasing excitatory transmission, but this effect was not blocked by gallamine. Microelectrophoretic application of cis-dioxolane and ES markedly increased the firing rate of dentate hilar interneurons and CA1 oriens/alveus interneurons and enhanced their synchrony to hippocampal theta rhythm. These findings suggest that select GABA-modulating neurosteroids and neuroactive estrogen sulfates alter septohippocampal cholinergic modulation of hippocampal GABAergic interneurons mediating recurrent, but not feedforward, inhibition of hippocampal principal cell activity.

Hippocampal Lesions Disrupt Navigation Based on the Shape of the Environment.

Geometric information provided by the walls of an environment has a strong influence over hippocampal unit activity. This suggests that the hippocampus forms part of a cognitive mapping system that encodes geometric relationships between environmental cues and the animal's location. Here, the authors show for the first time that excitotoxic lesions of the hippocampus disrupt the ability of rats to navigate to a goal using shape information provided by a solid-walled arena and an array of identical landmarks. These results are consistent with cognitive mapping theories of hippocampal function and extend previous research by showing that hippocampal cell loss impairs navigation with respect to shape information provided by both physical barriers and an array of landmarks.

Long-term plasticity in hippocampal place-cell representation of environmental geometry

The hippocampus is widely believed to be involved in the storage or consolidation of long-term memories. Several reports have shown short-term changes in single hippocampal unit activity during memory and plasticity experiments, but there has been no experimental demonstration of long-term persistent changes in neuronal activity in any region except primary cortical areas. Here we report that, in rats repeatedly exposed to two differently shaped environments, the hippocampal-place-cell representations of those environments gradually and incrementally diverge; this divergence is specific to environmental shape, occurs independently of explicit reward, persists for periods of at least one month, and transfers to new enclosures of the same shape. These results indicate that place cells may be a neural substrate for long-term incidental learning, and demonstrate the long-term stability of an experience-dependent firing pattern in the hippocampal formation.

Electrophysiological profile of avian hippocampal unit activity: a basis for regional subdivisions.

Electrophysiological activity was recorded from single neurons (units) in the hippocampal formation (HF) of freely moving homing pigeons in order to provide a taxonomy of unit types found in the avian HF; a taxonomy that could be used to define regional subdivisions and be compared with unit types found in the mammalian hippocampus. Two distinct types of unit were observed in the avian HF. One type was uniformly characterized by relatively rapid firing rates and shorter spike widths, and was found throughout the HF. The other type was more variable in activity profile but, compared with the fast-firing units, was characterized by slower firing rates and longer spike widths. However, despite the variable nature of the slow-firing units, most slow-firing units recorded within a given anatomical region displayed similar firing rates, spike widths, and interspike intervals. In general, ventral HF units displayed activity patterns similar to projection cells found in the mammalian Ammon's horn. Most dorsocaudal units displayed activity patterns similar to presumed granular cells in the mammalian dentate gyrus. By contrast, most dorsorostral units displayed activity patterns similar to a type of unit found in the mammalian subiculum. Although different in some details, the overall activity profile of units found in the avian HF, and their regional distribution, is strikingly similar to unit types found in the mammalian hippocampus, suggesting that unit activity profile is one hippocampal dimension conserved through evolution.

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.

The firing of hippocampal place cells predicts the future position of freely moving rats

Direct observation and automatic, video-based methods reveal that a large fraction of hippocampal pyramidal neurons recorded from freely moving rats behave as "place cells"; the firing of each place cell occurs almost exclusively when the rat is in a restricted part of its current environment. In earlier work, 2-dimensional firing distributions for place cells over the apparatus area were made under the assumption that the correct location for each spike was the animal's position at the instant that the spike was fired. Spatial firing distributions generated in this way often have a very simple structure, in which the single region of intense activity has a just one maximum, and where the rate decreases monotonically in all directions away from the maximum. We will refer to patterns of this sort as "ideal." We describe how the spatial firing pattern is altered by assigning spikes to positions earlier or later than the instant at which they were fired. Spatial firing distributions were generated for a range of constant displacements of the spike time-series against the position time series. Three quantitative measures were used to estimate the extent to which the spatial firing pattern at different "spike/position shifts" approximated the ideal pattern. The 3 measures are in agreement that spikes must precede the animal's position by about 120 msec for the spatial firing pattern to be closest to the ideal. These results suggest that hippocampal unit activity predicts the animal's future location on a short time scale.

Effects of hippocampal manipulations on the classically conditioned nictitating membrane response: Simulations by an attentional-associative model

The effects of various hippocampal manipulations on the classically conditioned nictitating membrane (NM) response were simulated by a real-time attentional-associative model. The model incorporates: (a) a mechanism capable of establishing associations between conditioned (CS) and unconditioned stimuli (US) and between two CSs, (b) a mechanism that combines CS-CS and CS-US associations and builds 'computational cognitive maps', (c) an attentional rule that 'tunes in' relevant CSs and 'tunes out' irrelevant CSs, (d) performance rules that convert learning variables into topography of the rabbit NM response, and (e) rules that convert learning variables into neuronal firing. The present study explored three hypotheses regarding hippocampal function: (a) hippocampal lesions (HL) impair the 'tuning out' of irrelevant stimuli, (b) hippocampal stimulation (HS) and hippocampal long-term potentiation (LTP) facilitate the 'tuning in' of relevant stimuli, and (c) hippocampal unit activity is proportional to the instantaneous value of associative variables that participate in the 'tuning' mechanisms. Computer simulations for the HL case were carried out for conditioning under different interstimulus intervals (ISI) with different types of US, discrimination reversal, and sensory preconditioning. Computer simulations for the HS and LTP case were carried out for acquisition of delay conditioning and of classical discrimination. In addition, simulations of hippocampal unit activity during acquisition and extinction are presented. Under the 'tuning out' hypothesis for the HL case, the model proved capable of simulating a large portion of the experimental data, showing discrepancies with relevant literature only when describing HL effects on trace conditioning with shock US under short and long ISIs, trace conditioning with air puff US under long ISIs, discrimination reversal and sensory preconditioning. Under the 'tuning in' hypothesis regarding the HS and LTP case, the model proved capable of simulating acquisition of delay conditioning but not acquisition of classical discrimination. Under the assumption that neuronal activity is proportional to the instantaneous value of associative variables, the model is able to simulate hippocampal unit activity.

The hippocampus and the classically conditioned nictitating membrane response: A real-time attentional-associative model

The present study introduces an attentional-associative model that incorporates (1) a mechanism capable of establishing associations between conditioned stimuli (CSs) and unconditioned stimuli (USs) and between two CSs; (2) a mechanism that, by combining CS-CS and CS-US associations, is capable of building a “computational cognitive map”; (3) a real-time version of Pearce and Hall’s (1980) attentional rule; (4) performance rules that convert learning variables into a topography of the rabbit’s nictitating membrane (NM) response; and (5) rules that convert learning variables into neuronal firing. The present study tested the “aggregate prediction” hypothesis as applied to hippocampal function. This hypothesis assumes that (1) the effect of hippocampal lesions (HL) is an impairment in the integration of the aggregate prediction used to compute attentional variables; (2) the effect of the induction of hippocampal long-term potentiation (LTP) is an increase in the value of the aggregate prediction by way of increasing the value of CS-CS associations; and (3) neural activity in the hippocampus is proportional to the instantaneous value of the aggregate prediction. In addition, the present study tested the hypothesis that medial septum activity is proportional to the value of attentional variables. Computer simulations for the HL case were carried out for acquisition under different interstimulus intervals, discrimination reversal, and sensory preconditioning. Computer simulations for the LTP case were carried out for discrimination acquisition. In addition, simulations of hippocampal unit activity during acquisition and extinction, and medial septum unit activity during the acquisition of conditioning, are presented. The aggregate prediction hypothesis proved capable of simulating most, but not all, experimental data regarding hippocampal manipulations in the rabbit’s NM response preparation.

Isapirone is a partial agonist at 5-hydroxytryptamine 1A (5-HT 1A) receptors in the rat hippocampus: electrophysiological evidence

Using iontophoretic techniques we observed that in vivo isapirone (TVX Q 7821), a selective ligand for the 5-HT 1A binding site, at low ejection currents (5–30 nA) antagonised 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (DPAT)-induced suppression of hippocampal unit activity, with little effect on baseline firing rate itself. At higher ejection currents (20–100 nA) or following prolonged application, isapirone inhibited unit firing. Responses to GABA were unaffected by isapirone. These data demonstrate that isapirone is a 5-HT 1A receptor antagonist with partial agonist properties on 5-HT sensitive neurones in the rat hippocampus.

Classical conditioning in 3-, 30-, and 45-month-old rabbits: Behavioral learning and hippocampal unit activity

Evidence has accumulated to suggest that the hippocampus is impaired by aging processes. Hippocampal multiple unit activity was examined in 3-, 30-, and 45-month-old rabbits during classical conditioning in the trace paradigm. Animals were trained daily with 126 paired trials of tone and airpuff. The 3-month-olds learned to a criterion of 8 9 CR's in a mean of 3.2 days, while the 30-month-olds took a mean of 9.4 days, and the 45-month-olds took a mean of 11.75 days. Neural unit activity in the hippocampus modeled the behavioral eyelid response but took much longer to develop in the older animals. Results suggest that rabbits as young as 2 1 2 years old show behavioral and correlated neural response deficits.

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.

Role of pentagstrin and oxytocin in dorsal hippocampal single unit activity during resultative and conflict-inducing feeding behavior in rabbits

The presence of pentagastrin in the perineuronal space of the dorsal hippocampus promotes selective involvement of the neurons of this region in the organization of goal-directed feeding behavior [2]. On the basis of P. K. Anokhin's theory of functional systems, it has be~n postulated that dominant excitation of feeding motivation extracts ~enetic information from memory by activation of certain regions of the genome of nerve cells coding a peptide factor which has a structure similar to that of gastrin.

ラットの海馬単一ニューロン活動と行動の対応関係

ラットの海馬単一ニューロン活動と行動の対応関係

Hippocampal unit response during temporal single alternation of classical conditioning with rewarding brain stimulation in the rat

To evaluate hippocampal function on working memory, an experiment of rewarding classical conditioning with a temporal single-alternation (SA) paradigm was conducted. White rats that showed positive self-stimulation to the lateral hypothalamus were trained on an SA schedule with 60-sec intervals, in which reinforced trials (R; CS-US) were regularly alternated with non-reinforced trials (N; CS alone). Unit activity from the hippocampus and the animals’ movements were recorded during the pairing of auditory CS and lateral hypothalamic stimulation (US). When the experimental schedule was shifted to SA from pseudoconditioning, the hippocampal unit activity increased in the CS periods on both R and N trials in the absence of behavioral response alternation. During SA training, hippocampal unit activity in the CS period significantly increased on R trials relative to N trials, when a differential behavioral response also appeared. No detectable differences in the hippocampal unit background pre-CS levels were found between R and N trials. The results are discussed in terms of the interaction between working memory and reference memory in the hippocampal function.

Hippocampal unit activity and delayed response in the monkey

Single unit activity was recorded from the hippocampus while Japanese monkeys ( Macaca fuscata, n = 4) were performing a delayed response (DR) task. A total of 272 units showed an obvious change in discharge rate in relation to the events of the DR task. These 272 related units were classified into 6 groups: cue-light related units ( n = 24), cue- and choice-light related units ( n = 41), choice-light related units ( n = 21), response-related units ( n = 51), reward-error units ( n = 17), and delay units ( n = 118). Reward-error units contained reward-related and error-related units. Error-related units showed changes in firing after incorrect responses and/or after omission of reward on correct trials. It is noteworthy that 43.4% of the related units are delay units which showed increased or decreased firing preferentially during the delay period. Some units showed a differential firing pattern during cue or delay period depending on the spatial position of the cue. The results of the present study are interpreted as an experimental evidence for the involvement of the hippocampus in DR task.

Unit activity of the septum and hippocampus transplanted alone or together into the anterior chamber of the rat eye

Unit activity of grafts of the septum and hippocampus, developing for 3–6 months in the anterior chamber of the eye was investigated in acute experiments on curarized orcerveau isole rats. Whereas neurons in the transplanted septum had spontaneous activity of irregular, regular, or rhythmic bursting type, activity was absent in hippocampal grafts or consisted of very infrequent synchronized population sites. If grafts of the septum and hippocampus developed together and contact was established between them, the same types of activity developed in the hippocampus as in the septum. In many paired grafts spontaneous epileptic phenomena were observed; they were easily provoked also by electrical stimulation of one of the grafts. Superfusion with medium with a high Mg++ concentration and low Ca++ concentration abolished spontaneous activity in most neurons of hippocampal but not septal grafts, and also suppressed some of the epileptic phenomena, evidence of the leading role of the septum in the organization of spontaneous hippocampal unit activity.

Action of ?-carboline derivatives on evoked hippocampal unit activity

Action of ?-carboline derivatives on evoked hippocampal unit activity