The vestibular sensory epithelia encode dynamic and static head movements in trains of action potentials that project to the central nervous system along primary afferent neurons. These signals provide the principal drive for behaviors such as the vestibulo-ocular reflex, which functions to stabilize visual gaze during head movements associated with dynamic behaviors, particularly during locomotion. While the response dynamics of vestibular afferents have been widely studied in a variety of animal models, the input/output relations have been limited to preparations that are restrained and/or anesthetized. Recent investigations using lower vertebrates have shown that peripheral vestibular stimulus processing is modulated by centrifugal efferent feedback driven by rostrally-projecting efference copy originating in spinal locomotor pattern generators. Therefore, critical insight into behaviorally-relevant peripheral vestibular stimulus processing would be gleaned under conditions of awake, behaving preparations. At present, data collected under these conditions do not exist. Therefore, such information requires the development of preparations in which the dynamic response characteristics of vestibular afferent neurons are investigated under conditions of natural locomotion. The present proposal aims to achieve this goal through the development of methods to record from individual vestibular afferent neurons in behaving chinchillas, agile rodents commonly used in studies of peripheral vestibular neurophysiology. There are two factors that support the use of this animal model for these studies: 1) the superior vestibular nerve can be accessed from the middle ear, precluding the need for an intracranial approach to the afferents; and 2) these animals tolerate chronic preparations very well. Critical to this project is the availability of a miniature electrophysiology platform that incorporates a 9 degree-of-freedom movement sensor along with a multichannel electrode headstage and on-board data storage. This hardware will enable the direct correlation of afferent discharge during head movements that occur during unrestrained natural locomotion. The successful development of these methods in an agile animal model will provide the foundation for future investigations of vestibular afferent dynamics under a variety of behavioral and treatment conditions, and will transcend the limitations of imposed upon our understanding of head movement coding by the constraints of passive stimulus presentation in restrained and/or anesthetized conditions. In so doing, the research aims of this application address the Functional Connectivity topic of research Priority Area 1 of the NIDCD Strategic Plan. In addition, the methods developed are seminal to understanding the role of vestibular sensory contributions to spatial navigation and orientation behaviors, and as such address other critical research priorities as identified in the Strategic Plan.

Public Health Relevance

? Public Health Relevance Central to most, if not all, locomotor behaviors is a specific goal utilizing one or more head-centric sensory systems (e.g. vision, olfaction, somatosensory, audition, etc.) as principal guides. The present exploratory investigation aims to develop and optimize methods to record from vestibular afferents in behaving preparations, which represent the foundation for future investigations concerning the mechanisms of peripheral stimulus processing by the vestibular epithelia. The development of this preparation would also represent a critical step toward understanding the coding of head movements that are integrated with other sensory modalities in the achievement of most goal-directed behaviors.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DC017285-02
Application #
9759915
Study Section
Auditory System Study Section (AUD)
Program Officer
Cyr, Janet
Project Start
2018-08-08
Project End
2020-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Surgery
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095