A5 noradrenergic-projecting C1 neurons activates sympathetic and breathing outputs in anesthetized rats

NEW FINDINGS What is the central question of this study? C1 neurons innervate pontine noradrenergic cell groups, including the A5 region. Therefore, our central question was to determine whether A5 noradrenergic neurons contribute to the activation of sympathetic and respiratory responses produced by selective activation of the C1 group of neurons. What is the main finding and its importance? We show that the increase in sympathetic and respiratory activities elicited by selective stimulation of C1 neurons are reduced after blockade of excitatory amino acid within the A5 region, suggesting that the C1-A5 pathway might be important for sympathetic-respiratory control. ABSTRACT Adrenergic C1 neurons innervate and excite pontine noradrenergic cells group, including the ventrolateral pontine noradrenergic region (A5). Here, we tested the hypothesis that C1 activates A5 neurons through the release of glutamate and this effect may be important to sympathetic and respiratory control. Using selective tools, we restricted the expression of the channelrhodopsin2 under the control of the artificial promoter PRSx8 to C1 neurons (69%). Transduced catecholaminergic terminals within the A5 region are in contact with noradrenergic A5 neurons and the C1 terminals within the A5 region are predominantly glutamatergic. In a different group of animals, we performed retrogradely lesion of C1 adrenergic projecting to A5 regions with unilateral injection of the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-DβH-SAP) directly into the A5 region during hypoxic condition. As expected, hypoxia (8% O2 - 3 hours) induced a robust increase in fos expression within the catecholaminergic C1 and A5 regions of the brainstem. Depletion of C1 cells projecting to A5 region reduced fos immunoreactive induced by hypoxia within the C1 region. Physiological experiments showed that bilateral injection of kynurenic acid (100 mM) into the A5 region reduced the rise in mean arterial pressure, sympathetic and phrenic nerves activities produced by optogenetic stimulation of C1 cells. In conclusion, the C1 neurons activate the ventrolateral pontine noradrenergic neurons (A5 region) possibly via the release of glutamate and might be important for sympathetic and respiratory outputs in anesthetized rats. This article is protected by copyright. All rights reserved.