Sympathoexcitatory role for neurons projecting from the mesencephalic locomotor region to the rostral ventrolateral medulla in rats

Abstract

C1 neurons in the rostral ventrolateral medulla (RVLM) are reportedly excited by voluntary exercise. The present study aimed to explore neural pathway(s) upstream to the RVLM that can play a role in sympathetic adjustments to exercise. First, via neuronal tracing experiments, we found that rat mesencephalic locomotor region (MLR), in which cholinergic neurons are abundantly distributed, sends direct projections to the RVLM (MLR‐RVLM neurons) since the MLR contained a number of neuronal cells immunoreactive to cholera toxin subunit B (CTb) that had been injected into the RVLM in advance (n = 8). It is noted that very few neurons immunoreactive to choline acetyltransferase in the MLR were labeled with CTb (n = 3), suggesting that the MLR‐RVLM neurons are not cholinergic. Next, we found that optogenetic stimulation of MLR‐RVLM neurons causes sympathoexcitation in rats. An AAV vector that encodes the channelrhodopsin variant, ChIEF‐tdTomato was bilaterally microinjected into the MLR (n = 7). More than 3 weeks later, bilateral photostimulation (473 nm wavelength, 10 mW, 40 Hz) provided to the RVLM of the anesthetized rats significantly (P < 0.05) elevated blood pressure. In another set of rats (n = 3), a retrograde AAV vector that encodes the channelrhodopsin‐GFP was bilaterally microinjected to the RVLM. In these rats, bilateral photostimulation of the MLR, in which a number of GFP‐labeled cell bodies were confirmed, significantly increased renal sympathetic nerve activity and blood pressure. Finally, confocal imaging revealed that MLR‐derived, tdTomato‐labeled axons containing VGLUT2 were closely associated with tyrosine hydroxylase‐positive neurons in the RVLM, suggesting that MLR‐RVLM glutamatergic neurons form synaptic contacts with RVLM C1 neurons. Based on these observations, we propose that excitation of MLR‐RVLM glutamatergic neurons contribute to sympathetic adjustments to exercise via stimulation of RVLM C1 neurons.Support or Funding InformationThis study was supported by JSPS KAKENHI 15H05367 (SK) & 16K15190 (SK); 16H05128 & 15H05932 (KN).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.