# The Role of Sensory Inputs and Cholinergic Modulation for the Coding of Location and Movement Speed in the Entorhinal Cortex

> **NIH NIH R00** · GEORGE MASON UNIVERSITY · 2024 · $378,974

## Abstract

PROJECT SUMMARY/ABSTRACT
 The goal of this project is to investigate potential mechanistic roles of sensory inputs and cholinergic
modulation for generating neural coding of location and movement speed. The results are expected to support
development of models of network mechanisms underlying psychiatric disorders. Representations for spatial
location and movement speed are important for path integration and memory-guided navigation. Recordings of
grid cells and theta oscillations in the medial entorhinal cortex in freely exploring mice under conditions of light
and complete darkness will first address the question how long the neuronal code for location by grid cell firing
and the code for movement speed by theta frequency are preserved in working memory in the absence of
visual inputs. Analysis of the acquired data will test the hypothesis that changes in spatial periodic grid cell
firing correlate in time with changes in the theta frequency vs. running speed relationship. The expected
outcomes of these analyses will be used to inform computational models of path integration, including models
of grid cell firing. Experiments under Specific Aim #2 will use fiber photometry for monitoring cholinergic activity
in the medial entorhinal cortex to address the role of cholinergic modulation in forming and preserving codes
for location and movement speed in the presence and absence of visual cues. Analyses will test if changes in
sensory inputs, neuronal activity, and cholinergic modulation correlate at different time scales. These analyses
will further our mechanistic understanding of coding principles underlying a broad range of cognitive processes
associated with spatial memory. Both grid cells and cholinergic modulation are essential in current models of
spatial memory and memory-guided navigation. Experiments under Specific Aim #3 will use optogenetic
inhibition of cholinergic projection neurons in the medial septum in combination with grid cell recordings in the
medial entorhinal cortex to test the hypothesis that cholinergic signaling is necessary for spatial periodic firing
of grid cells. Finally, experiments under Specific Aim #4 will investigate if auditory and olfactory cues are
sufficient to support the formation of a cognitive spatial map by grid cell firing in the medial entorhinal cortex.
Simultaneous recording of grid cells in the medial entorhinal cortex and monitoring of cholinergic activity by
fiber photometry in complete darkness during the presence or absence of auditory or olfactory cues will test the
hypotheses that auditory and olfactory inputs in isolation can be used to form a cognitive map that supports
path integration and that cholinergic modulation supports memory-guided navigation based on these maps.
 The experimental and computational skills developed during the training period of this project and the
additional theoretical training in neural data science and computational modeling will be crucial for the
accomplishment...

## Key facts

- **NIH application ID:** 10817768
- **Project number:** 5R00NS116129-05
- **Recipient organization:** GEORGE MASON UNIVERSITY
- **Principal Investigator:** Holger Dannenberg
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $378,974
- **Award type:** 5
- **Project period:** 2020-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817768

## Citation

> US National Institutes of Health, RePORTER application 10817768, The Role of Sensory Inputs and Cholinergic Modulation for the Coding of Location and Movement Speed in the Entorhinal Cortex (5R00NS116129-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10817768. Licensed CC0.

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