Neurogenic (vasovagal) syncope (VVS) is a significant medical problem. The faint is preceded by a Vasovagal Response (VVR), characterized by a sudden drop in arterial blood pressure (BP) and heart rate (HR). VVS and VVRs are diagnosed using a tilt test, a vestibular stimulus. Despite being relatively common, the neural basis of the VVR and the role of the vestibular system in inducing VVRs are not known. Moreover, there is no small animal model of VVRs. We recently showed that low frequency sinusoidal galvanic vestibular stimulation (sGVS) induces VVRs in anesthetized rats. As in humans, VVRs are also induced in rats by tilt. In the proposed research we will characterize the physiological properties of VVRs in rats, thereby establishing a useful small animal model of human VVRs. We propose that VVRs are induced by strong, repeated stimulation of the vestibulo-sympathetic reflex (VSR), which maintains blood flow to the brain during changes in head position relative to gravity.
Aim 1 will characterize the transitions from normal VSR to VVRs using pulses and sinusoids of galvanic stimulation to show that VVRs occur when the VSR is appropriately stimulated. Nose up tilt and Translation-While-Rotating (TWR) will be used to determine the axes of stimulation that are most likely to produce VVRs. Additionally, the low frequency oscillations in HR and BP that are produced by sGVS and tilt reflect activation of Mayer waves, thought to be of fundamental importance in maintaining BP stability.
In Aim 2 these oscillations will be modeled using a novel concept in which Mayer wave function is represented by a non-linear relaxation oscillator.
In Aim 3, single unit neurophysiological studies in otolith-recipient portions of the caudal vestibular nuclei will identify the functional characteristics and physiological signature of VVR- related neurons. Together, the proposed research will establish a model of VVS, document how the vestibular system controls BP, and demonstrate that VVRs are adaptive compensatory responses that serve to re- equilibrate BP after major perturbations.

Public Health Relevance

Vasovagal syncope (VVS;unexpected fainting) and vasovagal responses (VVR) are a significant medical problem when they recur frequently;the underlying causes and neural mechanisms that produce such fainting are unknown. We have recently shown that activation of the vestibular system causes arterial blood pressure and heart rate changes in anesthetized rats that are similar to the changes in humans during these faints. In this project, we will characterize the changes in blood pressure and heart rate that are produced by activation of the vestibular system with tilts and galvanic stimulation, model the process that is causing the faints with a novel relaxation oscillator, and investigate the underlying neuronal basis for these responses.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Sensorimotor Integration Study Section (SMI)
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Platt, Christopher
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Cohen, Bernard; Martinelli, Giorgio P; Xiang, Yongqing et al. (2017) Vestibular Activation Habituates the Vasovagal Response in the Rat. Front Neurol 8:83
Raphan, Theodore; Cohen, Bernard; Xiang, Yongqing et al. (2016) A Model of Blood Pressure, Heart Rate, and Vaso-Vagal Responses Produced by Vestibulo-Sympathetic Activation. Front Neurosci 10:96
Dai, Mingjia; Cohen, Bernard; Smouha, Eric et al. (2014) Readaptation of the vestibulo-ocular reflex relieves the mal de debarquement syndrome. Front Neurol 5:124
Yakushin, Sergei B; Martinelli, Giorgio P; Raphan, Theodore et al. (2014) Vasovagal oscillations and vasovagal responses produced by the vestibulo-sympathetic reflex in the rat. Front Neurol 5:37
Cohen, Bernard; Martinelli, Giorgio P; Raphan, Theodore et al. (2013) The vasovagal response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves. FASEB J 27:2564-72
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Cohen, Bernard; Yakushin, Sergei B; Holstein, Gay R (2012) What does galvanic vestibular stimulation actually activate: response. Front Neurol 3:148
Cohen, Bernard; Martinelli, Giorgio P; Ogorodnikov, Dmitri et al. (2011) Sinusoidal galvanic vestibular stimulation (sGVS) induces a vasovagal response in the rat. Exp Brain Res 210:45-55