R01AG073997

Aging and Dysfunction in the Peripheral Vestibular System - Project Summary

Vestibular dysfunction becomes more prevalent with age, and it is estimated that more than 80% of people over 80 years old experience dysfunction. Furthermore, approximately 8 million adults in the US suffer from balance impairment due to damage to the peripheral vestibular system, but effective treatments for balance dysfunction are virtually non-existent.

Vestibular hair cells within vestibular canal and otolith organs convert hair bundle motion into receptor potentials, and sensory information is relayed to the brain by action potentials in vestibular afferent nerves. Afferents in central zones of vestibular neuroepithelia exhibit different responses to vestibular stimuli than afferents in peripheral zones. There are three types of vestibular afferents: calyx-only afferents innervate one or more type I hair cells, bouton dendrites innervate type II hair cells, and dimorphic afferents contact both hair cell types. Calyx-only afferents are present only in central zones and have irregular firing patterns, whereas dimorphic afferents exist in both zones and have regular firing patterns.

We will study age-related dysfunction in calyx-bearing afferents in gerbil vestibular organs using novel preparations developed in the laboratories of the principal investigators. We will use electrophysiological, hair bundle stimulation, immunohistochemical, and behavioral approaches to address age-related changes in mature and aged vestibular epithelia.

In Aim 1, we will determine if functional changes in vestibular hair cell mechanotransduction and/or basolateral currents occur with age. Aim 2 will test the hypotheses that synaptic degeneration of calyx terminals will manifest as morphological uncoupling of type I hair cells from their associated calyces and deficits in vestibular evoked responses and behaviors. In Aim 3, we will directly investigate changes at the type I hair cell/calyx synapse by recording spontaneous activity and responses to hair bundle stimulation in mature and aged calyx afferents.

Our investigative team is uniquely positioned to carry out the proposed studies. Results from this work will provide new information on how the aging process impacts peripheral vestibular signals and may inform the development of vestibular neurotherapeutics targeting afferent nerves in order to restore normal vestibular function.

The Regents Of The Univ. Of Colorado

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Aurora, Colorado 800452507 United States

Single Zip Code

Central and Peripheral Control of Balance in Older Adults (R01 Clinical Trial Optional) (RFA-AG-21-011)

Amendment Since initial award the total obligations have increased 402% from $614,835 to $3,087,440.