# CRCNS: Role of mAChRs on CA 1 pyramidal neurons in memory formation and stability

> **NIH NIH R01** · MAX PLANCK FLORIDA CORPORATION · 2023 · $347,238

## Abstract

The formation and retention of memories of our daily experiences depend on a brain region called the 
hippocampus. Among the extensive neuromodulatory inputs the hippocampus receives, cholinergic inputs 
from the basal forebrain are crucial for learning and memory. These same inputs elicit reduced neuronal 
response with aging, and degenerate in patients suffering from Alzheimer's disease. Despite its critical 
role in memory formation and stability, how cholinergic modulation mediates memory functions through 
individual circuit elements in the hippocampus remains largely unknown. In CA 1, the major output of the 
hippocampus, acetylcholine receptors are expressed in multiple cell types and cellular compartments. 
Until now, it has been difficult to determine the contribution of individual elements to the overall network 
effects of acetylcholine. In this project, we will study the role of muscarinic cholinergic receptors located 
on the pyramidal neurons of the CA1 region in the formation and long-term stability of Internally 
Generated Sequences (IGS), the sequences generated during locomotion while sensory cues are held 
constant and as animals perform memory tasks. We will use IGS as a representative of memory-related 
activity patterns to reveal how cholinergic activity modulates the formation of and the long timescale drift 
in the hippocampal code and in turn refines the behavior by activating cell-type-specific acetylcholine 
receptors. Our experimental approach is to manipulate the strength and locus of cholinergic modulation in 
CA1 while imaging large numbers of neurons in awake head-fixed mice engaged in a 
hippocampus-dependent memory task. Specifically, we will selectively modulate the CA1 pyramidal 
neurons with cell-type specific neuropharmacological tools. Integrating computational modeling with 
findings from experiments, we will elucidate possible plasticity and network mechanisms responsible for 
the observed neuronal dynamics. By combining experimental and computational approaches to elucidate 
the cholinergic control of plasticity over memory formation and stability across the cellular, circuit, and 
behavioral levels, we will contribute novel insights into the effects of a disruption in cholinergic signaling. 
Our results may indicate which physiological parameters could be altered to compensate for the loss of 
cholinergic signals, and lead to the development of new treatment options for memory disorders.

## Key facts

- **NIH application ID:** 10831251
- **Project number:** 1R01AG085899-01
- **Recipient organization:** MAX PLANCK FLORIDA CORPORATION
- **Principal Investigator:** Yingxue Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $347,238
- **Award type:** 1
- **Project period:** 2023-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831251

## Citation

> US National Institutes of Health, RePORTER application 10831251, CRCNS: Role of mAChRs on CA 1 pyramidal neurons in memory formation and stability (1R01AG085899-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10831251. Licensed CC0.

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