Dissertation/Thesis Abstract

Modulation of Vestibular Efferents and Its Impact on Afferent Signalling in Live Animals
by Raghu, Vishal, Ph.D., State University of New York at Buffalo, 2019, 85; 22618815
Abstract (Summary)

The vestibular organs convey information about head tilt and movements to the brainstem and the cerebellum and control or influence powerful and fast reflexes, which allow us to maintain gaze and balance. The first stages of sensing happen in the three semicircular canals, which sense angular motion and the two otolith organs –the utricle and the saccule, which sense horizontal motion and vertical linear motions respectively. Vestibular afferent neurons can be broadly classified as regularly firing and irregularly firing based on their resting discharges. Irregular neurons form an important part of the phasic arc of the vestibular system that carries and processes information about high-frequency head motions

The vestibular periphery is also targeted by efferent feedback originating from the brainstem. While much is yet unknown about the exact nature of efferet-mediated modulations of hair cells and afferents, studying afferent properties via stimulation of efferent neurons have unearthed some important information about them. Broadly speaking, efferent-mediated afferent responses have the following characteristics in mammals: (i) efferent stimulation causes excitation in afferents (Marlinski et al., 2004), (ii) the responses consist of fast and slow components (iii) efferent stimulation lowers gains of afferent responses to movement (iv) the responses are more prominent in irregular afferents than in regular afferents, and (v) Strong head movements stimulate efferents which in turn reflect in afferent activity bilaterally. Efferents also play vitally important roles in mechanisms involved in vestibular plasticity such as compensation and adaptation, and it is believed that this happens via the influence efferents exert on the irregular/ phasic pathways in the vestibular system.

To thoroughly gain a deeper understanding of efferent action, it is necessary to study the independent functioning of both afferent and efferent neurons and the molecular signalling characteristics between efferents and their targets in a compartmentalized manner. For my first project, we used heat generated by optical radiation to inhibit efferents and observed its influence on the resting properties of vestibular afferents via single unit recording in-vivo. Opto-thermal inhibition of efferent fibers resulted in a profound inhibition of resting discharges of afferents particularly in irregular afferents, thus rendering them inadequate for signaling head movements. Thus, we concluded that efferent inputs are crucial for the irregular and hence the phasic pathway to exist in the first order of vestibular signaling.

The second goal of my thesis was to investigate the effects of pharmacological stimulation/ inhibition of efferent synapses in the bony labyrinth, on the gains elicited by afferents to jerk stimuli. For this, we designed a technique for rapid delivery of pharmacological agents to the vestibular inner ear epithelia and at the same time ensure its innocuousness. The technique involved performing an intracochlear injection close to the oval window via direct entry through the middle ear cavity. To confirm any lack of trauma to the vestibular functioning on the injected side, we measured vestibular sensory evoked potential (VsEP) amplitudes, latencies, and thresholds and found no difference between values before and after injection in the same animals. Additionally, the VsEP test shows that the injected AP, which is the same as the extracellular solution used in patch clamp recordings does not alter the ionic concentrations in the inner ear enough to cause a significant change in its functioning.

Thus, my research during my PhD training has provided new means to test the role of individual pathways of the vestibular efferent – afferent and efferent – hair cell synapses in normal vestibular functioning. The results obtained through these means delineate a crucial role for efferents to ensure the existence of normal resting discharges in vestibular afferents, especially the irregular afferents.

Indexing (document details)
Advisor: Sadeghi, Soroush G
Commitee: Slaughter, Malcolm, Xu-Friedman, Matthew, Salvi, Richard J
School: State University of New York at Buffalo
Department: Neuroscience
School Location: United States -- New York
Source: DAI-B 81/4(E), Dissertation Abstracts International
Subjects: Neurosciences
Keywords: Afferents, Efferents, Intracochlear injection, Optothermal inhibition, Vestibular system
Publication Number: 22618815
ISBN: 9781687961563
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