# Cholinergic modulation of olfactory coding.

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2024 · $460,908

## Abstract

Project Summary
Understanding how brain states influence sensory coding is fundamental in advancing our knowledge of the
mechanisms by which neural circuits encode sensory information. The basal forebrain cholinergic system has
long been implicated in such state changes and has been shown to play a crucial role in the detection, selection,
and processing of behaviorally relevant stimuli. However, to date, almost all work regarding cholinergic
modulation of olfactory circuits has focused on the effects of acetylcholine on olfactory system neurons while
largely ignoring the circumstances that drive cholinergic neuron activity. Thus, very little is currently known
regarding the conditions that drive basal forebrain cholinergic neuron activity or the characteristics of cholinergic
fiber activity within the olfactory bulb. Further, fundamental questions also remain regarding the primary function
of ACh release on olfactory coding, as most prior studies have focused on olfactory responses in anesthetized
mice. For example, in the olfactory bulb, acetylcholine release is thought to enhance the sensitivity of olfactory
bulb output cell odor responses and lead to improved olfactory discrimination. However, no experiments have
been performed directly addressing these hypothesized functions in awake animals, leaving acetylcholine’s
ultimate function within early olfactory regions unknown. The overall goal of this project is to understand this
process by investigating how sensory input, stimulus novelty, and odor discrimination drive olfactory projecting
cholinergic neuron activity and how this impacts olfactory odor responses. Our central hypothesis is that olfactory
projecting cholinergic neurons preferentially respond to novel stimuli and impart information regarding salience
to the olfactory circuits. We will use calcium imaging of defined cholinergic and olfactory system cell types
combined with chemogenetic manipulation in awake animals during well-characterized olfactory-mediated
behaviors to test this hypothesis. The findings of these experiments will be significant in that they will
fundamentally advance our knowledge of the function of cholinergic input during olfactory-related events, how
this affects sensory representations at multiple levels within the olfactory system, and how this ultimately impacts
olfactory perception and discrimination.

## Key facts

- **NIH application ID:** 10846615
- **Project number:** 5R01DC013779-08
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** MAX L FLETCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,908
- **Award type:** 5
- **Project period:** 2015-03-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10846615

## Citation

> US National Institutes of Health, RePORTER application 10846615, Cholinergic modulation of olfactory coding. (5R01DC013779-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10846615. Licensed CC0.

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