Abstract
The vestibulo-sympathetic reflex (VSR) actively modulates blood pressure during changes in posture. This reflex allows humans to stand up and quadrupeds to rear or climb without a precipitous decline in cerebral perfusion. The VSR pathway conveys signals from the vestibular end organs to the caudal vestibular nuclei. These cells, in turn, project to pre-sympathetic neurons in the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). The present study assessed glutamate- and GABA-related immunofluorescence associated with central vestibular neurons of the VSR pathway in rats. Retrograde FluoroGold tract tracing was used to label vestibular neurons with projections to RVLM or CVLM, and sinusoidal galvanic vestibular stimulation (GVS) was employed to activate these pathways. Central vestibular neurons of the VSR were identified by co-localization of FluoroGold and cFos protein, which accumulates in some vestibular neurons following galvanic stimulation. Triple-label immunofluorescence was used to co-localize glutamate- or GABA- labeling in the identified VSR pathway neurons. Most activated projection neurons displayed intense glutamate immunofluorescence, suggestive of glutamatergic neurotransmission. To support this, anterograde tracer was injected into the caudal vestibular nuclei. Vestibular axons and terminals in RVLM and CVLM co-localized the anterograde tracer and vesicular glutamate transporter-2 signals. Other retrogradely-labeled cFos-positive neurons displayed intense GABA immunofluorescence. VSR pathway neurons of both phenotypes were present in the caudal medial and spinal vestibular nuclei, and projected to both RVLM and CVLM. As a group, however, triple-labeled vestibular cells with intense glutamate immunofluorescence were located more rostrally in the vestibular nuclei than the GABAergic neurons. Only the GABAergic VSR pathway neurons showed a target preference, projecting predominantly to CVLM. These data provide the first demonstration of two disparate chemoanatomic VSR pathways.
Highlights
Homeostatic control of blood pressure is mediated by the baroreflex, a highly effective closed-loop negative feedback pathway responsible for maintaining stable blood pressure (Hall, 2016)
FluoroGold-filled perikarya were observed in the caudal VNC of all 17 rats with tracer injections restricted to rostral ventrolateral medulla (RVLM) or caudal ventrolateral medulla (CVLM)
Legend: Approximate Bregma levels of the tracer injection site (Center) and the rostral and caudal extent of the diffusion penumbra in RVLM or CVLM of all rats used for the multiple label immunofluorescence studies of cFos- and FluoroGoldpositive neurons
Summary
Homeostatic control of blood pressure is mediated by the baroreflex, a highly effective closed-loop negative feedback pathway responsible for maintaining stable blood pressure (Hall, 2016). More direct and rapid modulation of blood pressure in response to head movements and other postural adjustments is achieved through interactions between vestibular end organ-activated neurons in the vestibular nuclei and presympathetic brainstem cell groups, including RVLM and CVLM (Yates and Bronstein, 2005) These vestibulo-sympathetic reflex (VSR) pathways provide a proactive mechanism for initiating blood redistribution in the body during movement or changes in posture in order to assure consistent cerebral perfusion (Yates, 1996; Kerman et al, 2000b) regardless of head position (Yates and Miller, 1994; Woodring et al, 1997; Balaban and Yates, 2004; Abe et al, 2009; Nakamura et al, 2009)
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