# Linking Plasticity of Hippocampal Representation across the Single Neuron and Circuit Levels

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $487,347

## Abstract

Functional interactions between the entorhinal cortex and hippocampus are critical for spatial navigation
and episodic memories related to people, places, objects and events. Canonically, medial entorhinal
cortex (MEC) processes spatial information while lateral entorhinal cortex (LEC) processes non-spatial
contextual information. This ‘where’ and ‘what’ information is then projected to the hippocampus for
formation of long-term representations associating the sensory and spatial features of the environment.
Flexibility in hippocampal representations is critical for generating adaptive learnt behaviors and relies on
plasticity. We propose a new role for entorhinal cortex in modulating hippocampal plasticity and spatial
representations. To test this, we will dissociate the lesser known organization and function of long-range and
local circuit dialogue between LEC vs. MEC and area CA3 of hippocampus during spatial coding.
The PI (Basu) and co-PI (Clopath), both early stage investigators, are combining their complementary
expertise in experimental and computational approaches to build an integrated circuit centric model of
plasticity in the hippocampus across multiple levels. This study will test the hypothesis that beyond the
classically biased role of LEC inputs in non-spatial coding, coordinated activity of glutamatergic and newly
discovered GABAergic input (Basu et al., 2016) from both LEC and MEC is necessary for context-dependent
plasticity of hippocampal place cells via gating of local excitation-inhibition dynamics and dendritic integration.
To test this idea, we have established innovative set of tools on the experimental and computational fronts to
examine place cell plasticity across multiple levels. We will perform intracellular electrophysiology from soma
and dendrites of CA3 neurons in acute slices to functional map the LEC-CA3 circuit (Aim 1), and read out CA3
place cell behavior at sub-cellular resolution with in vivo two-photon imaging of CA3 soma and dendrites as
well as LEC axons in behaving animals during a head-fixed context morphing spatial navigational task (Aim 2).
In collaboration with Dr. Cliff Kentros, we will develop LEC cell type specific mouse lines for multiplexed
optogenetic activation and silencing of glutamatergic and GABAergic inputs simultaneously or alternatingly and
read-out how these manipulations impact CA3 plasticity. We are building a unique computational model of
hippocampal place cell coding at single neuron (Aim 1) and network (Aim 2) levels incorporating modulation of
dendritic excitation-inhibition and long-term plasticity (Bono and Clopath 2010). Drs. György Buzsáki and
Dmitry Chklovskii will provide expert consultation on place cell and large-scale imaging data analysis.
Our study will provide a unique perspective on long-range and local circuit dynamics that impart flexibility to
otherwise stable neuronal representations of space based on environmental demands. This will help better
identify circuits...

## Key facts

- **NIH application ID:** 9955377
- **Project number:** 5R01NS109994-03
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Jayeeta Basu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $487,347
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955377

## Citation

> US National Institutes of Health, RePORTER application 9955377, Linking Plasticity of Hippocampal Representation across the Single Neuron and Circuit Levels (5R01NS109994-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9955377. Licensed CC0.

---

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