# The Receptor Basis for Serotonergic Modulation of Olfaction Across Multiple BrainAreas

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2021 · $70,023

## Abstract

Project Summary. Sensory networks continuously fine-tune how they process information to meet ongoing
physiological demands. The nervous system achieves this flexibility via the release of “neuromodulators” which
alter the biophysical and synaptic properties of individual neuron classes within a network. This adjusts the
influence of each class to optimize network dynamics for the appropriate context. Neuromodulation is
ubiquitous and many neurological disorders result from, or are associated with, dysfunctional neuromodulatory
systems. Despite the importance of neuromodulation for healthy sensory processing, our ability to predict the
consequences of neuromodulation is limited by the diversity of modulatory receptors expressed by different
classes of neurons. Each receptor has different effects and each class of neuron supports different features of
sensory coding, so the effects of neuromodulation can be complex. We propose to address this issue in a
genetically tractable model with fewer neurons and modulatory receptors; the olfactory system of Drosophila.
The objective of this application is to determine how serotonin (5-HT) receptor subtypes affect key neuronal
classes and the consequences for olfactory processing and odor-guided behavior. The long-term goal of this
research is to determine the mechanistic basis for neuromodulation of sensory network dynamics.
 In vertebrate and invertebrate olfactory systems, the effects of 5-HT on odor-evoked responses vary
across different neuron classes. However, it is difficult to determine how 5-HT alters olfactory processing
without knowing the consequences of activating the 5-HT receptors expressed by each class. We recently
completed a comprehensive atlas of 5-HT receptor expression within the olfactory system, so we now propose
to manipulate the expression of individual 5-HT receptors in specific classes of neurons to determine how 5-HT
affects individual neuron classes, the consequences for odor coding across olfactory brain regions and odor-
guided behavior. In addition, we will use one of the first whole brain, nanometer resolution EM connectomes to
establish single cell resolution connectivity rules of 5-HT neurons with each olfactory neuron class examined in
this proposal. In Specific Aim 1 we will determine the receptor basis for the effects of 5-HT on local inhibitory
networks within the first olfactory neuropil (the antennal lobe or “AL”). In Aim 2 we will determine the
contribution of direct modulation of cholinergic AL output neurons to the overall effects of 5-HT on olfactory
information sent to downstream processing stages. Finally, in Aim 3 we will determine how 5-HT receptors
modulate GABAergic AL output neurons that promote olfactory attraction. These experiments will establish
how the overall effects of 5-HT emerge from neuron class-specific expression of 5-HT receptors, thus
addressing a critical gap in our knowledge of healthy sensory processing.

## Key facts

- **NIH application ID:** 10424907
- **Project number:** 3R01DC016293-04S1
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Andrew M Dacks
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,023
- **Award type:** 3
- **Project period:** 2018-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424907

## Citation

> US National Institutes of Health, RePORTER application 10424907, The Receptor Basis for Serotonergic Modulation of Olfaction Across Multiple BrainAreas (3R01DC016293-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10424907. Licensed CC0.

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