Hippocampal Cell Assemblies Research Articles

Oscillatory Heritage of the Grastyán School

Two major structural designs characterize the cerebral cortex: the scalable, modular neocortex and the single-module hippocampus. Functions attributed to the hippocampal formation have varied over the past several decades and include episodic memory in human lesion studies, spatial mapping in single unit recordings and voluntary exploration of the environment in field recording studies in animals. I suggest that the common thread across these parallel developments is that each captures the essence of episodic coding: items are organized in spatio-temporal context. I suggest that theta oscillations, studied extensively in the Grastyan school in Pecs, is the key temporal metric. Ordered sequences of items are encoded by the strict temporal relations of hippocampal cell assemblies nesting within cycles of theta oscillation. Such a temporal compression mechanism brings neuronal assemblies together in the time window of synaptic plasticity and allows the linking of first order (neighbor) and higher order relat...

Temporal Encoding of Place Sequences by Hippocampal Cell Assemblies

Both episodic memory and spatial navigation require temporal encoding of the relationships between events or locations. In a linear maze, ordered spatial distances between sequential locations were represented by the temporal relations of hippocampal place cell pairs within cycles of theta oscillation in a compressed manner. Such correlations could arise due to spike "phase precession" of independent neurons driven by common theta pacemaker or as a result of temporal coordination among specific hippocampal cell assemblies. We found that temporal correlation between place cell pairs was stronger than predicted by a pacemaker drive of independent neurons, indicating a critical role for synaptic interactions and precise timing within and across cell assemblies in place sequence representation. CA1 and CA3 ensembles, identifying spatial locations, were active preferentially on opposite phases of theta cycles. These observations suggest that interleaving CA3 neuronal sequences bind CA1 assemblies representing overlapping past, present, and future locations into single episodes.

Encoding New Episodes and Making Them Stick

How do we encode, store, and retrieve new episodic memories, and what are the computations performed by the hippocampus during this process? One system that has been used to model the brain basis of episodic memory in humans is the study of spatial navigation by path integration in rodents. Here I discuss three exciting new findings focused on encoding or replay of spatial sequences in the rat hippocampus. These findings not only provide important new insight into the computations associated with encoding and consolidation of spatial trajectories, but may also have implications for understanding key aspects of human episodic memory.

Place-Selective Firing of CA1 Pyramidal Cells during Sharp Wave/Ripple Network Patterns in Exploratory Behavior

We observed sharp wave/ripples (SWR) during exploration within brief (<2.4 s) interruptions of or during theta oscillations. CA1 network responses of SWRs occurring during exploration (eSWR) and SWRs detected in waking immobility or sleep were similar. However, neuronal activity during eSWR was location dependent, and eSWR-related firing was stronger inside the place field than outside. The eSPW-related firing increase was stronger than the baseline increase inside compared to outside, suggesting a "supralinear" summation of eSWR and place-selective inputs. Pairs of cells with similar place fields and/or correlated firing during exploration showed stronger coactivation during eSWRs and subsequent sleep-SWRs. Sequential activation of place cells was not required for the reactivation of waking co-firing patterns; cell pairs with symmetrical cross-correlations still showed reactivated waking co-firing patterns during sleep-SWRs. We suggest that place-selective firing during eSWRs facilitates initial associations between cells with similar place fields that enable place-related ensemble patterns to recur during subsequent sleep-SWRs.

Progressive Transformation of Hippocampal Neuronal Representations in “Morphed” Environments

Hippocampal neural codes for different, familiar environments are thought to reflect distinct attractor states, possibly implemented in the recurrent CA3 network. A defining property of an attractor network is its ability to undergo sharp and coherent transitions between pre-established (learned) representations when the inputs to the network are changed. To determine whether hippocampal neuronal ensembles exhibit such discontinuities, we recorded in CA3 and CA1 when a familiar square recording enclosure was morphed in quantifiable steps into a familiar circular enclosure while leaving other inputs constant. We observed a gradual noncoherent progression from the initial to the final network state. In CA3, the transformation was accompanied by significant hysteresis, resulting in more similar end states than when only square and circle were presented. These observations suggest that hippocampal cell assemblies are capable of incremental plastic deformation, with incongruous information being incorporated into pre-existing representations.

Theta rhythm of navigation: Link between path integration and landmark navigation, episodic and semantic memory

Five key topics have been reverberating in hippocampal-entorhinal cortex (EC) research over the past five decades: episodic and semantic memory, path integration ("dead reckoning") and landmark ("map") navigation, and theta oscillation. We suggest that the systematic relations between single cell discharge and the activity of neuronal ensembles reflected in local field theta oscillations provide a useful insight into the relationship among these terms. In rats trained to run in direction-guided (1-dimensional) tasks, hippocampal cell assemblies discharge sequentially, with different assemblies active on opposite runs, i.e., place cells are unidirectional. Such tasks do not require map representation and are formally identical with learning sequentially occurring items in an episode. Hebbian plasticity, acting within the temporal window of the theta cycle, converts the travel distances into synaptic strengths between the sequentially activated and unidirectionally connected assemblies. In contrast, place representations by hippocampal neurons in 2-dimensional environments are typically omnidirectional, characteristic of a map. Generation of a map requires exploration, essentially a dead reckoning behavior. We suggest that omnidirectional navigation through the same places (junctions) during exploration gives rise to omnidirectional place cells and, consequently, maps free of temporal context. Analogously, multiple crossings of common junction(s) of episodes convert the common junction(s) into context-free or semantic memory. Theta oscillation can hence be conceived as the navigation rhythm through both physical and mnemonic space, facilitating the formation of maps and episodic/semantic memories.

Communication between neocortex and hippocampus during sleep in rodents.

Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves/slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical-hippocampal interplay may be important for memory consolidation.

Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat

This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model. Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.

Reactivation of Hippocampal Cell Assemblies: Effects of Behavioral State, Experience, and EEG Dynamics

During slow wave sleep (SWS), traces of neuronal activity patterns from preceding behavior can be observed in rat hippocampus and neocortex. The spontaneous reactivation of these patterns is manifested as the reinstatement of the distribution of pairwise firing-rate correlations within a population of simultaneously recorded neurons. The effects of behavioral state [quiet wakefulness, SWS, and rapid eye movement (REM)], interactions between two successive spatial experiences, and global modulation during 200 Hz electroencephalographic (EEG) "ripples" on pattern reinstatement were studied in CA1 pyramidal cell population recordings. Pairwise firing-rate correlations during often repeated experiences accounted for a significant proportion of the variance in these interactions in subsequent SWS or quiet wakefulness and, to a lesser degree, during SWS before the experience on a given day. The latter effect was absent for novel experiences, suggesting that a persistent memory trace develops with experience. Pattern reinstatement was strongest during sharp wave-ripple oscillations, suggesting that these events may reflect system convergence onto attractor states corresponding to previous experiences. When two different experiences occurred in succession, the statistically independent effects of both were evident in subsequent SWS. Thus, the patterns of neural activity reemerge spontaneously, and in an interleaved manner, and do not necessarily reflect persistence of an active memory (i.e., reverberation). Firing-rate correlations during REM sleep were not related to the preceding familiar experience, possibly as a consequence of trace decay during the intervening SWS. REM episodes also did not detectably influence the correlation structure in subsequent SWS, suggesting a lack of strengthening of memory traces during REM sleep, at least in the case of familiar experiences.

Hippocampal and neocortical cell assemblies encode memory processes for different types of stimuli in the rat

The objective of this study was to determine whether each of several different memory processes is encoded exclusively by specific single neurons (single-neuron coding) or by overlapped groups of neurons (population coding by cell assembly). Single neuronal activity was recorded from the rat hippocampal formation (CA1, CA3, dentate gyrus) and temporal cortex during the performance of simple auditory, simple visual, and configural auditory-visual discrimination tasks. All the tasks employed the identical apparatus and time parameters and differed only in the type of stimuli to be processed for correct performance. Single neurons showing significantly differential activity among the discriminative stimuli in each task were judged to be task-related and involved in the memory process of the task. Of the total number of neurons recorded from the hippocampal formation and temporal cortex, 21-26% of the neurons showed task-related activity in only one task, in two tasks, or in all three tasks. This result indicates some overlapping among the neurons involved in each of teh different memory processes. A cross-correlation analysis tested activity correlations among the neurons recorded simultaneously. Most pairs of the hippocampal neurons related to the same tasks (same memory processes) showed correlations during performance of the related tasks. This result showing coactivation of the same types of task-related neurons, together with the result showing the overlapping of task-related neurons, supports the concept of population coding by cell assemblies specifically in the hippocampal formation during memory processing.

Cross-Correlation Analysis of Interneuronal Connectivity in cat visual cortex.

Cross-Correlation Analysis of Interneuronal Connectivity in cat visual cortex.