Neuroscience and Neurobiology Commons^™

Trpm4 Ion Channels In Pre-Bo¨Tzinger Complex Interneurons Are Essential For Breathing Motor Pattern But Not Rhythm, Marina Cristina D. Picardo, Yae K. Sugimura, Kaitlyn E. Dorst, Prajkta S. Kallurkar, Victoria T. Akins, Xingru Ma, Ryoichi Teruyama, Romaine Guinamard, Kaiwen Kam, Margaret Saha, Christopher A. Del Negro

Christopher Del Negro

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and …