# Memory computations across hippocampal, entorhinal, and prefrontal circuits

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $407,507

## Abstract

PROJECT SUMMARY
A combination of entorhinal, hippocampal, and prefrontal pathology has a pivotal role in most neurological
and neurodegenerative diseases and in the emergence of memory impairments that are associated with these
diseases. Despite the knowledge that these brain regions are particularly vulnerable, the diversity of neural
computations within and across these brain regions is only beginning to be revealed. For example, a key
function of the hippocampus and medial entorhinal cortex (mEC) is to bridge events that are discontinuous in
time, and entorhinal and hippocampal cells that are sequentially active (‘time cells’) have been proposed to be
pivotal for memory retention over delay intervals of many seconds. In our previous work, we therefore
investigated the firing patterns over the delay interval in a spatial working memory (WM) task. We
unexpectedly found that hippocampal time cells were not a general mechanism for WM retention in
hippocampus-dependent tasks. Rather, preliminary data indicate that information about past and future
choices during the delay interval is evident during brief population bursts in hippocampus, while mEC cells
may show memory-related activity that persists irrespective of brain state. We therefore hypothesize that
memory retention does not require time-varying activity over the delay interval but is rather evident in
sporadic population bursts in hippocampus and medial prefrontal cortex (mPFC) throughout the delay period
and in firing patterns of entorhinal cells that provide continuity irrespective of brain state. To record activity
during the delay period with varying brain states, we will – within each animal – use two variants of a spatial
WM task, one with and one without forced running throughout the delay such that either theta or non-theta
states are predominant. Aim 1 will focus on population bursts in hippocampus and determine whether they are
only informative in non-theta states, as shown in our preliminary data, or a general mechanism across brain
states. In addition, we will selectively interrupt hippocampal activity within the delay period to determine
whether coding of future choices by population bursts and behavior are perturbed. Aim 2 will then perform
recordings across deep and superficial layers and along the dorso-ventral axis of entorhinal cortex to identify
how mEC contributes to WM. Finally, Aim 3 will carry out large-scale combined single-unit and LFP recordings
in hippocampus and mPFC and in mEC and mPFC to reveal the coordination of mechanisms for WM retention
across brain regions and brain states. Taken together, we will identify whether neuronal activity during
population bursts is a general mechanism for memory retention over delay intervals irrespective of brain state,
whether mEC supports WM retention with persistent activity, and how subregions of mPFC are coordinated
with hippocampal and entorhinal subareas along the dorso-ventral axis. Identifying these memory
computatio...

## Key facts

- **NIH application ID:** 10153897
- **Project number:** 5R01NS086947-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Stefan Leutgeb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $407,507
- **Award type:** 5
- **Project period:** 2014-03-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153897

## Citation

> US National Institutes of Health, RePORTER application 10153897, Memory computations across hippocampal, entorhinal, and prefrontal circuits (5R01NS086947-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153897. Licensed CC0.

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