# Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $511,179

## Abstract

PROJECT SUMMARY
The baroreflex is a homeostatic feedback pathway responsible for maintaining stable blood flow to the brain.
Baroreceptor signals are conveyed to the solitary nucleus and then to the caudal ventrolateral medulla
(CVLM). The CVLM sends both excitatory and GABAergic inhibitory projections to the rostral ventrolateral
medulla (RVLM), which in turn provides the key input to preganglionic sympathetic neurons in the spinal cord
that control sympathetic nerve activity. The baroreflex pathway is polysynaptic, has a relatively long latency,
and is solely reactive, modulating vasoconstriction and heart rate in response to a prior cardiovascular
vicissitude such as a change in blood pressure (BP). In contrast, the vestibulo-sympathetic reflex (VSR)
mediates proactive, direct and rapid BP modulation, initiating blood redistribution in the body at the onset of
movement or a postural adjustment in order to assure consistent cerebral perfusion regardless of head
position. The VSR is triggered by input from the vestibular end organs, which convey signals to neurons in the
caudal vestibular nuclei (VNc) that project to CVLM and/or RVLM. Activation of this pathway through VNc
causes changes in sympathetic nerve activity and BP. We have recently found that there are two limbs of the
VSR, one that is GABAergic and putatively inhibitory, and another that is putatively excitatory and
glutamatergic. The goal of the proposed research is to determine the specific connectivity of these two
chemoanatomic facets of the VSR using a novel approach to activate individual end organs. testing the overall
hypothesis that the direction of BP change resulting from stimulation reflects the differential activation,
connectivity and synaptology of these two main limbs of the VSR. The project takes advantage of the spatial
specificity of pulsed infrared laser stimulation of the vestibular end organs in order to discretely activate
individual receptor regions. We will test the hypotheses that focal stimulation restricted to the utricle or saccule
activates specific chemoanatomically-defined subtypes of VSR neurons that are topographically segregated
within the VNC and project primarily to either RVLM or CVLM. In addition, we will investigate the effects of
combined utricular, saccular and posterior semicircular canal activation on BP mediated by the VSR.
Ultrastructural studies will be conducted to confirm the detailed anatomy of this pathway. Overall, this project
addresses the anatomical bases for VSR responses, and is foundational for establishing the utility and efficacy
of infrared laser stimulation as a next-generation treatment for vestibulo-autonomic disorders including
neurogenic orthostatic hypotension and intolerance.

## Key facts

- **NIH application ID:** 9893847
- **Project number:** 5R01DC008846-12
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Gay R Holstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $511,179
- **Award type:** 5
- **Project period:** 2008-03-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893847

## Citation

> US National Institutes of Health, RePORTER application 9893847, Chemical Anatomy and Synaptology of Vestibulo-Sympathetic Pathways (5R01DC008846-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893847. Licensed CC0.

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