# Cortical feedback and olfactory processing

> **NIH NIH R01** · HARVARD UNIVERSITY · 2020 · $359,125

## Abstract

A key problem in sensory neuroscience is how nervous systems can detect objects of interest in noisy and
cluttered sensory scenes, which then guide further action. This ability to pick out important information from
the array of mixed stimuli is thought to involve extensive top-down modulation that interacts with
feedforward processing of information. We propose to investigate this important function in the olfactory
system of behaving mice using optogenetic and optophysiological methods. Olfaction is critical for the
survival of many animals, which use this sense for to find food and mates, and to avoid predators.
Information about volatile odorants sensed by olfactory sensory neurons is passed on to the olfactory bulb
(OB), whose output reaches many cortical directly areas. This feedforward architecture is disrupted by
massive feedback connections throughout the olfactory system, which are thought to provide context and
learning-related signals to aid in odor perception. We recently developed an odor-guided behavioral task in
which mice are required to parse complex odorous stimuli. In this project, we will use this exciting new
behavioral assay to examine the role of cortical feedback to the OB in the genetically-accessible mouse
model. To achieve our goals, we will first characterize how complex odor mixtures are represented in the
OB, and then examine the effects of selective optogenetic perturbation of cortical feedback projections on
the coding of complex odor stimuli in the OB. Then using a suite of cutting-edge methods already
established in our group, we will uncover how the feedback signals conveyed to the OB evolve as mice
learn to perform this task. Experiments in this project will be guided by three Aims. Aim 1: To determine
how the output neurons of the OB represent odorant mixtures and how they are altered after mice learn the
mixture task. Aim 2: To determine the effects of selective optogenetic perturbation of olfactory cortical
neuron activity on odor coding in OB output neurons. Aim 3: To determine the features of stimulus-related
signals carried by cortical feedback axons to the OB in naïve mice and in mice that have learnt the mixture
task. The research proposed has broad relevance for neuroscience because it will shed light on how brains
interpret ambiguous sensory stimuli in cluttered environments, an ability that is thought to involve top-down
feedback. This ability is thought to be impaired with aging, as well as in some mental disorders. Therefore,
understanding this process in the normal brain could help devise specific and efficacious treatments in
abnormal conditions.

## Key facts

- **NIH application ID:** 9872146
- **Project number:** 5R01DC016289-03
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** VENKATESH N MURTHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $359,125
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872146

## Citation

> US National Institutes of Health, RePORTER application 9872146, Cortical feedback and olfactory processing (5R01DC016289-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872146. Licensed CC0.

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