Studies completed in this laboratory during the past several years have contributed to our understanding of two closely related questions in auditory research: 1) How do inhibitory amino acids function within known brainstem auditory circuits to encode acoustic information? 2) What is the impact of aging on inhibitory amino acid neurotransmission in the auditory brainstem? Studies of this nature have made significant inroads into the nature of presbycusis, a major disorder among the aged and may lead to pharmacological treatment strategies for age-related hearing loss. In vivo iontophoretic and in vitro studies in cochlear nucleus (CN) and inferior colliculus (IC) have revealed that inhibitory amino acid neurotransmitters are critically involved in the control of dynamic range, echo suppression and detection of signal in noise. Recent studies from this laboratory suggest that circuits within the CN and IC undergo age-related changes associated with inhibitory neurotransmission. The current proposal will extend this strong foundation of work by carrying out the following proposed studies: 1) microiontophoresis to examine the role of the inhibitory amino acid GABA in shaping responses to amplitude modulated sinusoids in the IC; 2) neurochemical techniques to further characterize age-related changes in the molecular nature of the GABAA receptor; and 3) single unit physiology to examine age-related changes in the response properties of DCN fusiform cells.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC000151-21
Application #
6175788
Study Section
Hearing Research Study Section (HAR)
Program Officer
Freeman, Nancy
Project Start
1979-08-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
21
Fiscal Year
2000
Total Cost
$183,307
Indirect Cost
Name
Southern Illinois University School of Medicine
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Springfield
State
IL
Country
United States
Zip Code
62794
Cai, Rui; Montgomery, Scott C; Graves, Kaley A et al. (2018) The FBN rat model of aging: investigation of ABR waveforms and ribbon synapse changes. Neurobiol Aging 62:53-63
Sottile, Sarah Y; Hackett, Troy A; Cai, Rui et al. (2017) Presynaptic Neuronal Nicotinic Receptors Differentially Shape Select Inputs to Auditory Thalamus and Are Negatively Impacted by Aging. J Neurosci 37:11377-11389
Caspary, Donald M; Llano, Daniel A (2017) Auditory thalamic circuits and GABAA receptor function: Putative mechanisms in tinnitus pathology. Hear Res 349:197-207
Sottile, Sarah Y; Ling, Lynne; Cox, Brandon C et al. (2017) Impact of ageing on postsynaptic neuronal nicotinic neurotransmission in auditory thalamus. J Physiol 595:5375-5385
Cai, Rui; Richardson, Ben D; Caspary, Donald M (2016) Responses to Predictable versus Random Temporally Complex Stimuli from Single Units in Auditory Thalamus: Impact of Aging and Anesthesia. J Neurosci 36:10696-10706
Stebbings, K A; Choi, H W; Ravindra, A et al. (2016) Ageing-related changes in GABAergic inhibition in mouse auditory cortex, measured using in vitro flavoprotein autofluorescence imaging. J Physiol 594:207-21
Sametsky, Evgeny A; Turner, Jeremy G; Larsen, Deb et al. (2015) Enhanced GABAA-Mediated Tonic Inhibition in Auditory Thalamus of Rats with Behavioral Evidence of Tinnitus. J Neurosci 35:9369-80
Cai, R; Caspary, D M (2015) GABAergic inhibition shapes SAM responses in rat auditory thalamus. Neuroscience 299:146-55
Cai, Rui; Kalappa, Bopanna I; Brozoski, Thomas J et al. (2014) Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus? J Neurophysiol 111:229-38
Henry, James A; Roberts, Larry E; Caspary, Donald M et al. (2014) Underlying mechanisms of tinnitus: review and clinical implications. J Am Acad Audiol 25:5-22; quiz 126

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