Eupnea & Sigh

Joint work with Christopher A. Del Negro.

In collaboration with Del Negro and jointly mentored graduate students, we are developing biologically realistic mathematical models of the neural origins of breathing behavior. Under normal physiological conditions, breathing consists of eupnea, the periodic pumping movements that ventilate the lung for gas exchange, and sighs, larger but less frequent breaths that optimize gas exchange efficiency or express emotion.

Even though their frequencies differ by orders of magnitude, eupnea- and sigh-related rhythms originate in the preBötzinger Complex (preBötC), a specialized medullary site that is necessary and sufficient to generate breathing movements in vivo. Analogous motor output pertaining to eupnea and sigh can be recorded from slice preparations that retain the preBötC and hypoglossal (XII) motoneurons, which have inspiratory function.

Slices encapsulate a complete breathing microcircuit that generates eupnea and sigh, which is experimentally advantageous for interrogating rhythmogenic mechanisms in vitro. The overall aim of this project is to determine the cellular and synaptic mechanisms of eupnea and sigh rhythms, using a combination of modeling and experiment, with a focus on the neural mechanisms that couple these rhythms.

News

• “That was terrifying:” Ph.D. student begins research career by unsettling “settled science”, by Joseph McClain.

Prior Work

• Borrus D, Grover C, Conradi Smith GD, Del Negro CA. The preBötzinger complex generates sigh rhythm via intracellular calcium oscillations in mice. In preparation, 2021.
• Kallurkar PS, Picardo MCD, Sugimura YK, Saha MS, Conradi Smith GD, Del Negro CA. Transcriptomes of electrophysiologically recorded Dbx1-derived respiratory neurons of the preBötzinger complex in neonatal mice. Submitted to Genome Biology. [BioRxiv preprint]
• Borrus D, Conradi Smith GD, Del Negro CA. Role of synaptic inhibition in the coupling of the respiratory rhythms that underlie eupnea and sigh behaviors. eNeuro 7(3):1-20, 2020. [10.1523/ENEURO.0302-19.2020] [PMID:32393585]

Funding

National Center for Complementary & Integrative Health (NCCIH), joint NSF-NIH program Collaborative Research in Computational Neuroscience (CRCNS). Discovering the neural mechanisms of breathing rhythms - eupnea and sigh. PIs: Christopher Del Negro and Greg Conradi Smith. 1R01AT01816-01. 8/19-7/22.