R01DC019459

Peripheral Vestibular Hypofunction and Neurosensory Coding - Project Summary

The proposed research addresses critical issues of high translational importance concerning the mechanisms and outcomes of partial dysfunction of the vestibular sensory epithelia, referred to as peripheral vestibular hypofunction. The research plan utilizes chemotoxin-induced hypofunction, the foundation for which was identified through recent work from the PI's laboratory in an animal model enabling precise intraperilymphatic dosing resulting in the production of highly reproducible lesions. This provides the basis for producing lesions of graded magnitudes within the sensory neuroepithelia, documented through histopathologic analyses.

The physiologic outcome of these lesions will be evaluated through recordings of single afferent neuron electrophysiology and the vestibulo-ocular reflex, providing the bases for establishing histologic and physiologic correlates to a direct behavioral test of vestibular function. Previous work has demonstrated that the afferent neuron calyx is highly labile to pathologic compromise, and owing to its important contribution to shaping neural dynamics in untreated epithelia, it is a focus for assessing pathologic damage.

The present research plan will enable the direct correlate of afferent discharge dynamics to critical cellular components of the calyx, including its morphology and expression of KCNQ4 and sodium-potassium ATPase. In addition, we will examine the distribution of synaptic ribbons within hair cells of lesioned epithelia, testing whether a systematic synaptopathy also contributes to the compromised vestibular function.

In summary, the present investigation provides critical insight into the histopathologic substrates of vestibular hypofunction and the alterations in sensory coding that underlie the functional compromise. At the same time, however, this investigation will reveal important cellular and physiologic metrics that are required for normal vestibular function, addressing longstanding questions in vestibular neurobiology.

Los Angeles University Of California

TO INVESTIGATE SOLUTIONS TO PROBLEMS DIRECTLY RELEVANT TO INDIVIDUALS WITH DEAFNESS OR DISORDERS OF HUMAN COMMUNICATION IN THE AREAS OF HEARING, BALANCE, SMELL, TASTE, VOICE, SPEECH, AND LANGUAGE. THE NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS (NIDCD) SUPPORTS RESEARCH AND RESEARCH TRAINING, INCLUDING INVESTIGATION INTO THE ETIOLOGY, PATHOLOGY, DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES, PRIMARILY THROUGH THE SUPPORT OF BASIC AND APPLIED RESEARCH IN ANATOMY, AUDIOLOGY, BIOCHEMISTRY, BIOENGINEERING, EPIDEMIOLOGY, GENETICS, IMMUNOLOGY, MICROBIOLOGY, MOLECULAR BIOLOGY, THE NEUROSCIENCES, OTOLARYNGOLOGY, PSYCHOLOGY, PHARMACOLOGY, PHYSIOLOGY, PSYCHOPHYSICS, SPEECH-LANGUAGE PATHOLOGY, AND OTHER SCIENTIFIC DISCIPLINES. THE NIDCD SUPPORTS: (1) RESEARCH INTO THE EVALUATION OF TECHNIQUES AND DEVICES USED IN DIAGNOSIS, TREATMENT, REHABILITATION, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES; (2) RESEARCH INTO PREVENTION AND EARLY DETECTION AND DIAGNOSIS OF HEARING LOSS AND SPEECH, VOICE, AND LANGUAGE DISORDERS AND RESEARCH INTO PREVENTING THE EFFECTS OF SUCH DISORDERS BY MEANS OF APPROPRIATE REFERRAL AND REHABILITATION; (3) RESEARCH INTO THE DETECTION, TREATMENT, AND PREVENTION OF DISORDERS OF HEARING AND OTHER COMMUNICATION PROCESSES IN THE ELDERLY POPULATION AND ITS REHABILITATION TO ENSURE CONTINUED EFFECTIVE COMMUNICATION SKILLS; AND (4) RESEARCH TO EXPAND KNOWLEDGE OF THE EFFECTS OF ENVIRONMENTAL AGENTS THAT INFLUENCE HEARING OR OTHER COMMUNICATION PROCESSES.

93.173 - Research Related to Deafness and Communication Disorders

National Institute on Deafness and Other Communication Disorders (NIDCD) [HHS - NIH]

Los Angeles, California 90095 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the End Date has been extended from 04/30/26 to 04/30/27 and the total obligations have increased 373% from $642,108 to $3,037,920.