# Cortical feedback and olfactory processing

> **NIH NIH R01** · HARVARD UNIVERSITY · 2020 · $199,275

## Abstract

Summary for the supplemental request
 Olfactory dysfunction is often a first symptom of several neurodegenerative diseases, including
Alzheimer's disease (AD). Therefore, an improved understanding of how the neural circuitry and functional
properties of the olfactory system are altered in models of AD may provide clues to the etiology of AD, as well
as potential diagnostic readouts. In the olfactory system, feedback projections from the olfactory cortex to the
olfactory bulb may play a critical role in both the detection and analytical processing of odor stimuli. These
same projections may be particularly sensitive to AD progression due to their anatomical interface between the
olfactory bulb and cortex, two sites of early disease progression. We will test the hypothesis that in a mouse
model of AD, disease-related disruption of the morphology and stimulus coding properties of top-down
projections to the olfactory bulb impairs olfactory function. In Supplemental Aim 1 we will monitor changes in
morphological features of cortical projections to the olfactory bulb through AD-like progression. In
Supplemental Aim 2 we will measure the functional properties of feedback projections using naturalistic odor
stimuli, combined with in vivo multiphoton imaging and behavioral readouts. These aims are closely aligned
with Parent Grant Aim 3, where we will measure the activity of cortical projections to the olfactory bulb to
determine how these projections contribute to neural pattern separation and behavioral accuracy on
naturalistic odor mixture tasks. The results of our supplemental studies will extend our understanding of the link
between AD-like progression and olfactory impairment in two fundamental ways. First, we will gain new insight
to the structure and function of long-range projections from the cortex to the olfactory bulb in the context of
disease progression. Second, because olfactory dysfunction typically precedes the onset of other disease-
related symptoms, we will begin to uncover the breakdown in stimulus coding that may predict a decline in
perceptual accuracy that accompanies AD progression. The results we obtain from the completion of this
project will provide the basis for future experiments related to plasticity and stimulus discrimination in the
context of AD pathology.

## Key facts

- **NIH application ID:** 10118416
- **Project number:** 3R01DC016289-03S1
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** VENKATESH N MURTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $199,275
- **Award type:** 3
- **Project period:** 2020-04-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118416

## Citation

> US National Institutes of Health, RePORTER application 10118416, Cortical feedback and olfactory processing (3R01DC016289-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10118416. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*