Acute intermittent optogenetic stimulation of nucleus tractus solitarius neurons induces sympathetic long-term facilitation

Am J Physiol Regul Integr Comp Physiol. 2015 Feb 15;308(4):R266-75. doi: 10.1152/ajpregu.00381.2014. Epub 2014 Dec 17.

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.

Keywords: nucleus tractus solitarius; optogenetics; sympathetic long-term facilitation; synchronization.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Animals
  • Baroreflex
  • Blood Pressure
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Channelrhodopsins
  • Disease Models, Animal
  • Heart Rate
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia / physiopathology*
  • Kidney / innervation*
  • Light
  • Long-Term Potentiation*
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Optogenetics / methods*
  • Photic Stimulation
  • Phrenic Nerve / drug effects
  • Phrenic Nerve / metabolism
  • Phrenic Nerve / physiopathology*
  • Rats, Sprague-Dawley
  • Red Fluorescent Protein
  • Respiration
  • Solitary Nucleus / drug effects
  • Solitary Nucleus / metabolism
  • Solitary Nucleus / physiopathology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*
  • Time Factors

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Channelrhodopsins
  • Luminescent Proteins
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2