# Characterizing Direct Cortical Influences on Hippocampal CA1 Population Dynamics in Behaving Mice

> **NIH NIH F31** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $45,520

## Abstract

The mammalian hippocampus plays critical roles in navigation and episodic memory. The most prominent
hippocampal neural correlate of these behaviors is “place cell” activity: during spatial exploration, a subset of
excitatory principal neurons in the hippocampus fire in restricted regions of the environment (termed ‘‘place
fields’’). At the population level, place cells form internal maps of the external environment, which are thought to
also support hippocampal memory functions. Indeed, place cell maps have been shown to dynamically
reorganize in response to novel sensory cues, changes in the multi-sensory environmental context, and in
particular, in response to salient features of the environment, such as appetitive reward signals during goal-
oriented spatial learning. It is widely assumed that afferent excitatory inputs to the hippocampus carry critical
information required for these navigational and memory-related changes in hippocampal network dynamics. Two
subregions of the Entorhinal Cortex (EC) have been particularly implicated in this process by providing dual input
streams to the hippocampus. Specifically, the medial EC (MEC) is thought to be involved in primarily processing
spatial information related to global contextual reference frame, while the lateral EC (LEC) is thought to primarily
process information related to individual items and locations based on a local reference frame. Nevertheless, a
detailed understanding of the circuit level mechanisms of entorhinal cortical influences on hippocampal
population dynamics is still lacking with conflicting experimental results showing varying degree of deficits in
navigational and memory behaviors following EC manipulations. This deficiency largely stems from the lack of
available information on (1) the specific type of information conveyed directly by identified EC afferents to the
hippocampus, (2) the experience-dependent changes in information carried by EC projections, and (3) changes
in EC signaling in response to relative novelty and salience of the sensory environment. The MEC and LEC
direct projections to pyramidal cells (CA1PCs) in the mouse dorsal hippocampal CA1 area offers a tractable
circuit to bridge this knowledge gap by leveraging chronic, subcellular-resolution two-photon functional imaging
of identified EC afferents and CA1PCs during head-fixed virtual reality navigation and learning. These
experiments will test the hypothesis that CA1PCs receive direct spatial, sensory and salience-related information
from identified EC inputs which instruct CA1PCs population dynamics depending on behavioral task demands.
Aim 1 will use chronic calcium imaging of EC axonal inputs in CA1 to characterize what information is carried by
the MEC and LEC direct projections to CA1 and analyze how their activity changes over time related to novelty
and behavioral salience. Aim 2 will employ simultaneous calcium imaging from EC axons and CA1 pyramidal
cells (CA1PCs), as well as optogenetic mani...

## Key facts

- **NIH application ID:** 9988525
- **Project number:** 5F31NS110316-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** John Bowler
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2018-09-13 → 2021-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988525

## Citation

> US National Institutes of Health, RePORTER application 9988525, Characterizing Direct Cortical Influences on Hippocampal CA1 Population Dynamics in Behaving Mice (5F31NS110316-03). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9988525. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*