title: Acute intermittent optogenetic stimulation of nucleus tractus solitarius neurons induces sympathetic long-term facilitation.
abstract: Acute intermittent hypoxia (AIH) induces sympathetic and phrenic long-term facilitation (LTF), defined as a sustained increase in nerve discharge. We investigated the effects of AIH and acute intermittent optogenetic (AIO) stimulation of neurons labeled with AAV-CaMKIIa, hChR2(H134R), and mCherry in the nucleus of the solitary tract (NTS) of anesthetized, vagotomized, and mechanically ventilated rats. We measured renal sympathetic nerve activity (RSNA), phrenic nerve activity (PNA), power spectral density, and coherence, and we made cross-correlation measurements to determine how AIO stimulation and AIH affected synchronization between PNA and RSNA. Sixty minutes after AIH produced by ventilation with 10% oxygen in balanced nitrogen, RSNA and PNA amplitude increased by 80% and by 130%, respectively (P < 0.01). Sixty minutes after AIO stimulation, RSNA and PNA amplitude increased by 60% and 100%, respectively, (P < 0.01). These results suggest that acute intermittent stimulation of NTS neurons can induce renal sympathetic and phrenic LTF in the absence of hypoxia or chemoreceptor afferent activation. We also found that while acute intermittent optogenetic and hypoxic stimulations increased respiration-related RSNA modulation (P < 0.01), they did not increase synchronization between central respiratory drive and RSNA. We conclude that mechanisms that induce LTF originate within the caudal NTS and extend to other interconnecting neuronal elements of the central nervous cardiorespiratory network.
authors.affiliation: Department of Integrative Physiology, Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; and.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Peter
authors.initials: P
authors.lastname: Lalley
authors.affiliation: Department of Integrative Physiology, Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, Texas; and Steve.Mifflin@unthsc.edu.
authors.forename: Steve
authors.initials: S
authors.lastname: Mifflin
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex; D001794:Blood Pressure; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D000075402:Channelrhodopsins; D004195:Disease Models, Animal; D006339:Heart Rate; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation*; D008027:Light; D017774:Long-Term Potentiation; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D012119:Respiration; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D000097573:Red Fluorescent Protein
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000075402:Channelrhodopsins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein
keywords: nucleus tractus solitarius; optogenetics; sympathetic long-term facilitation; synchronization