Special Lecture by Jayeeta Basu

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Hippocampal pyramidal neurons function as place cells by exhibiting location-specific modulation of activity during navigation. Place cells are hypothesized to serve as the neural substrate for long-term episodic memory of space, with distinct place cell ensembles representing distinct environments. Yet we have limited knowledge about how these representations emerge during learning, and whether learned place maps stabilize with memory consolidation. To fill in this gap, here we examined behaviorally driven organization of place cell activity during memory formation and recall. We designed an operant head-fixed spatial navigation task that imposed demands on spatial, contextual, and episodic aspects of memory behavior, and imaged hundreds of pyramidal neurons in dorsal CA1 across all phases of learning. We found that place cells are rapidly recruited into task-dependent spatial maps, resulting in emergence of both orthogonal and overlapping representations of space. Further, task-selective place cells use a diverse set of remapping strategies to represent changing task demands, such as reward goals and trial-dependent trajectories that accompany learning. Individual neuron maps and decoding of population data showed prominent divergence of spatial map representations between trial types during learning, with a remarkably strong correlation to task performance. Finally, imaging during remote memory recall (up to 30 days) revealed increased stabilization of learned place cell maps following memory consolidation. Our study reveals that place maps rapidly evolve their activity dynamics at the cellular and ensemble levels to represent various features of the environment and the experience as a function of learning. Once formed, behaviorally driven place maps show long-term stability, supporting a role for hippocampal-dependent recall of contextually-rich spatial memories. To understand circuit mechanisms that may allow for association of contextual, and episodic features upon the spatial map, in another study we explored the role of lateral entorhinal cortex inputs in gating dendritic spikes. Dendritic spikes have been postulated to be an underlying cellular mechanism for plasticity and feature selective tuning such as context dependent place cell formation. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. LEC provides multisensory inputs about odors, objects, novelty and rewards to distal dendrites of CA1 pyramidal neurons. We found using slice electrophysiology and functional circuit mapping that optogenetic stimulation of LEC glutamatergic input is capable of driving local dendritic spikes in hippocampal pyramidal neurons. This dendritic spike generation is promoted by cortical recruitment of a local VIP interneuron-mediated disinhibitory microcircuit. Our results highlight new circuit mechanisms by which dynamic interaction of excitation, inhibition, and disinhibition support supralinear single-cell computations, which may allow context dependent coding of place cells.