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

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $396,156

## Abstract

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.

## Key facts

- **NIH application ID:** 10620709
- **Project number:** 5R01MH126904-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Lisa Giocomo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $396,156
- **Award type:** 5
- **Project period:** 2022-05-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10620709

## Citation

> US National Institutes of Health, RePORTER application 10620709, The Dynamics of Neural Representations for Distinct Spatial Contexts and Memory Episodes (5R01MH126904-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10620709. Licensed CC0.

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