The Dynamics of Neural Representations for Distinct Spatial Contexts and Memory Episodes

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A central function of the brain is to create internal representations of stimuli and experiences from the outside world to guide behavior. Here, we examine the circuit mechanisms underlying the neural representation of external space, a representation essential to spatial memory and navigation, and impacted by neurodegenerative and psychiatric diseases. The neural basis for the representation of space depends, in part, on circuits in the medial entorhinal cortex (MEC), which contains neurons that encode the spatial position, orientation and running speed of an animal. Between distinct environments, the firing fields of position and orientation cells can change their firing rate and rotate or move to a new spatial location – phenomenon known as ‘remapping’. Together with other structures in the parahippocampal region, MEC neurons can generate unique neural representations for distinct environments, potentially contributing to the encoding of different contexts or episodes. While remapping in MEC has often been studied between environments that differ in sensory features (i.e. visual or odor cues), we have found in recent and preliminary data that behavioral variables (i.e. running speed, expectation of reward) can evoke internal transitions between neural population states (i.e. remapping) in MEC. Here, we aim to test the hypotheses that a change in behavioral variables can drive transitions in MEC neural population states via key nodes in entorhinal circuitry (Aim 1) and that behaviorally driven MEC spatial maps are optimized to represent features relevant to the navigational behavior executed in the environment (Aim 3). Moreover, we aim to establish causality between changes in behavioral variables and transitions in MEC neural population states (Aim 2). To address these aims, we propose to combine electrophysiology using silicon probes with spatial and memory tasks in behaving mice. Until now, electrophysiological approaches had to contend with limited recording channel counts, contributing to a lack of studies that considered MEC neural coding at the population level or as a function of behavioral variables. However, new versions of silicon probes have allowed us to record hundreds of MEC neurons simultaneously along nearly the entire length of mouse entorhinal cortex. This, combined with virtual reality tasks that can provide dense sampling of sensory and behavioral variables, as well as optogenetic perturbations to establish causality between changes in behavioral variables and transitions in MEC neural population states, will enable us to achieve significant new insight into the mechanisms underlying transitions in MEC neural population states and the of such transitions in supporting memory and navigation.