# Mechanisms of olfactory signal processing

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2023 · $414,482

## Abstract

Project Summary/Abstract
(ASDs)
an
Individuals
communication,
can
spectrum disorders
results from the loss of expression of the Fragile X mental retardation protein (FMRP),
mRNA-binding protein encoded on the X chromosome involved in suppressing protein translation.
with FXS can exhibit a range of debilitating deficits in cognitive abilities, social interactions and
 and sensory processing. Deficits in sensory processing, often observed as hypersensitivity,
contribute to other deficits associated with FXS (e.g., in social interactions). The
Fragile X syndrome (FXS) is the single most common monogenetic cause of autism
in humans. FXS
broad objective of this
proposal is to examine dysfunction in the olfactory system of mouse models for Fragile X with reduced
expression of the mouse gene for FMRP, Fmr1. Surprisingly, despite the overwhelming importance of olfaction
for rodents, there are few studies in this sensory modality in Fmr1 KO mice. Our goals, divided across three
Aims, will be:
Aim 1: To test the hypothesis that Fmr1 regulates inhibitory synaptic connections in the bulb.
Aim 2: To test the hypothesis that Fmr1 regulates local network activity in the bulb by controlling inhibitory
synaptic connections.
Aim 3. To test the hypothesis that Fmr1 regulates olfactory behavior and bulbar oscillations in awake behaving
mice by controlling inhibitory synaptic connections.
 Our studies will utilize a variety of approaches including patch-clamp recordings in brain slices,
ultrastructural analyses, behavioral experiments, and in vivo electrophysiological recordings. Mouse models
will include whole-animal Fmr1 KO mice, which is the most widely used mouse model of FXS, along with
conditional KO and recovery mice in which Fmr1 expression is selectively and inducibly manipulated in
GAD65-expressing GABAergic interneurons. This multidisciplinary approach will enable us to identify
dysfunction in olfaction that results from altered Fmr1 expression at levels ranging from single synapses to
whole-animal behavior and also link the changes observed at the different levels.

## Key facts

- **NIH application ID:** 10604284
- **Project number:** 5R01DC006640-18
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** NATHAN Eric SCHOPPA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $414,482
- **Award type:** 5
- **Project period:** 2005-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10604284

## Citation

> US National Institutes of Health, RePORTER application 10604284, Mechanisms of olfactory signal processing (5R01DC006640-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10604284. Licensed CC0.

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