# Olfactory Modulation of Respiration-Entrained Brain Activity and Behavior

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $479,348

## Abstract

Project Summary
Breathing patterns have strong impacts on emotions in humans. Voluntary control of respiration, especially via
nasal breathing as practiced in yoga and meditation, is effective in reducing anxiety, stress, or even panic
attacks. The effects of breathing patterns on emotions are thought to be related to respiration-entrained brain
rhythms, which have been recognized for decades, but their sources and functions remain elusive. One
potential source of respiration-entrained brain activity is the olfactory system. Nasal airflow activates
intrinsically mechanosensitive olfactory sensory neurons (OSNs) in the nose, which carry the information to the
olfactory bulb (OB) and subsequently to the olfactory cortical regions including the anterior olfactory
nucleus/taenia tecta (AON for simplicity). It is well known that the neural activity along the olfactory pathway is
highly correlated with respiration. Interestingly, recent studies indicate that many non-olfactory cortical and
limbic structures including the medial prefrontal cortex (mPFC) also display nasal airflow-dependent,
respiration-entrained oscillations in both rodents and humans. A potential role of respiration-entrained neural
activity has been examined in the context of learned fear, an emotional state inferred by quantifiable freezing
behavior in rodents. During fear retrieval after tone-foot shock pairing, mice freeze to the conditioned tones
while breathe at a steady rate (~4 Hz), which is correlated with a predominant 4-Hz oscillation in the mPFC, a
region critical for expression of conditioned fear. Disruption of peripheral olfactory inputs significantly reduces
the 4-Hz oscillation in the mPFC and leads to prolonged freezing periods. However, the neural circuits
underlying the effects of olfactory inputs on the mPFC activity and fear-related behaviors remain largely
unresolved. We recently discovered that the mPFC receives direct inputs from the AON, a major target of the
OB tufted cells, which receive stronger peripheral inputs and display robust respiration-entrained activity. The
central hypothesis of this proposal is that the OB tufted cellsAONmPFC pathway is the critical neural
circuit in modulating the mPFC respiration-related rhythm and relevant behaviors. Multidisciplinary approaches
(gene editing, ex vivo and in vivo electrophysiology, optogenetics, circuit tracing, and behavior) will be
combined to pursue three specific aims. We will (1) dissect out this neural pathway in a cell-type specific
manner, (2) determine functional properties of this pathway, and (3) determine behavioral effects of
optogenetic manipulations of this pathway. Overall, the current study will provide critical insights into olfactory
modulation of respiration-entrained brain activity and behavior.

## Key facts

- **NIH application ID:** 10071517
- **Project number:** 2R01DC006213-16A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Minghong Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $479,348
- **Award type:** 2
- **Project period:** 2004-03-05 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071517

## Citation

> US National Institutes of Health, RePORTER application 10071517, Olfactory Modulation of Respiration-Entrained Brain Activity and Behavior (2R01DC006213-16A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071517. Licensed CC0.

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