Cellular and circuit mechanisms of volitional breath-holding

Active Project Grant Awarded Last action

Award ID
F31HL182436
Recipient
Awarding agency
Obligated
$43,101

Award facts

Assistance listing
93.837 Cardiovascular Diseases Research
Completion date 0% complete
Place of performance
San Francisco, CA 94143, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
The breathing and heart rhythms are both essential for life, but unlike the incessant beating of the heart, breathing has the unique capacity to be stopped at will. From our first breath, innate protective reflexes can pause breathing, needed in instances like a sudden immersion into water. Eventually, we learn to volitionally stop or modify our breathing for various purposes. This includes learning to preemptively hold our breath, as in preparation for a dive, or to avoid noxious odors rather than depending upon reflexes. Another is the capacity to use our breath to express emotions, like a sigh of frustration, or adopting a slow breathing pattern to alleviate stress. This ability to control such a vital behavior epitomizes volition. Despite this evident importance, the mechanisms that allow US to override this autonomous behavior remain elusive. Here, we aim to determine whether a volitional breath hold is executed by engaging conserved reflex pathways that stop breathing, or whether the brain employs an entirely new approach. We have developed a novel pavlovian-like conditioning task to teach mice to voluntarily hold their breath for the equivalent of humans pausing their breathing for ~45 seconds. Briefly, training involves pairing a neutral odor (e.g., lemon) with an ammonia puff that reflexively pauses breathing. After several days, mice hold their breath in response to lemon alone. This robust task, coupled with the advanced murine genetic and viral tools to study the nervous system, offers a powerful platform to perform a detailed dissection of the neural circuits that are used for learning and stopping breathing. The focus of this proposal is to determine how the volitional breath hold is executed (aim 1) and how the mouse learns to do so (aim 2). Aim 1 will use a combination of in vivo multi-electrode electrophysiological recordings and optogenetic manipulations to determine whether the learned breath-hold is achieved by silencing the breathing pacemaker or by inhibiting downstream premotor or motor pathways. Aim 2 will firmly establish the primary sensory signal that is used to learn volitional breath-holding, examining the roles of lung, chemosensory, olfactory, and trigeminal sensory inputs engaged in this task. The insights gained from this research will not only elucidate how the brain overrides automatic control of breathing but will also establish a foundation for understanding how other rhythmic, innate actions, such as vocalization, chewing, and swallowing, become volitionally commanded. Furthermore, this work paves the way to study whether other learned breathing patterns, such as slow, calming breaths, can be taught and utilized to alleviate conditions like anxiety and panic disorders. By advancing our understanding of volitional control over breathing, this research holds the potential to inform behavioral and therapeutic strategies for individuals struggling with disorders of breathing, emotion regulation, and cardiovascular health.

Transactions

Action Obligated Date
Amendment $0
Original award $43,101

Quick answers

Who received award F31HL182436?

F31HL182436 was awarded to The Regents Of The University Of California. San Francisco by National Heart Lung and Blood Institute (National Institutes of Health) on December 15, 2026.

How much is award F31HL182436 worth?

$43,101 has been obligated on F31HL182436.

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