Auditory Neuropharmacology:

Age-related hearing loss (presbycusis) is a complex state which may reflect pathological influences along the entire auditory system. For certain kinds of age-related hearing loss, there is a dramatic loss of speech understanding without a parallel loss in pure-tone thresholds. This loss is especially severe under noisy conditions. Central auditory dysfunction in aging may be in response to partial peripheral deafferentation and may be similar to changes observed with noise exposure or ototoxic drugs. In many ways, the underlying causes of tinnitus, the hearing of phantom sounds, may also reflect changes due to the partial deafferentation of the central auditory processor. These changes may involve changes in the synthesis, degradation, uptake, release and receptor sensitivity of neurotransmitter systems. Studies in our laboratory are focused on the understanding of two closely related questions in auditory research:

1. How do inhibitory neurotransmitters function within known auditory circuits to encode acoustic information?
2. What is the impact of aging and tinnitus on inhibitory neurotransmission throughout the central auditory system?

   Studies in most central auditory structures have found that inhibitory neurotransmitters are critically involved in coding acoustic information. Coding of these signals appears vulnerable to the aging process and to the peripheral damage frequently observed in tinnitus. Studies of circuits within the central auditory system undergo age-related and tinnitus-related changes to pre and postsynaptic GABAergic and glycinergic neurotransmission. Ongoing projects in the laboratory are focused on how the brain changes its ability to process auditory signals as we age and in animal models of tinnitus. Neurochemical and molecular studies are examining how receptors in auditory structures change their structural makeup with the partial deafferentation seen in aging and tinnitus. We also examine the mechanisms which trigger these receptor changes. A clear understanding of plastic changes within central auditory circuits could lead to the development of pharmacotherapy for tinnitus and for age-related hearing loss.

Techniques:

• In vivo auditory system single unit electrophysiology with iontophoresis
• In vivo auditory system multi channel recordings in awake animals
• In vitro patch clamp studies of thalamic and cortical auditory structures
• Quantitative receptor binding studies
• Molecular protein chemistry
• In situ hybridization
• Immunohistological studies/confocal microscopy

Coding studies:

• Iontophoretic studies of auditory system
• Aging electrophysiology studies
• Aging neurochemical studies of the auditory neuraxis
• Western blotting of receptor subunit proteins and glutamic acid decarboxylase
• In situ hybridization of receptor subunit proteins
• Receptor binding/pharmacology of the GABAA receptor
• Chloride flux/age-related changes in GABAA receptor function

Recent Publications:

Plasticity at glycinergic synapses in dorsal cochlear nucleus of rats with behavioral evidence of tinnitus.
Wang H, Brozoski TJ, Turner JG, Ling L, Parrish JL, Hughes LF, Caspary DM.
Neuroscience. 2009 Dec 1;164(2):747-59. Epub 2009 Aug 20.PMID: 19699270 [PubMed - in process] Related articles >

Processing of broadband stimuli across A1 layers in young and aged rats.
Hughes LF, Turner JG, Parrish JL, Caspary DM.
Hear Res. 2009 Sep 20. [Epub ahead of print]PMID: 19772906 [PubMed - as supplied by publisher] Related articles >

Age-related changes in glycine receptor subunit composition and binding in dorsal cochlear nucleus.
Wang H, Turner JG, Ling L, Parrish JL, Hughes LF, Caspary DM.
Neuroscience. 2009 Apr 21;160(1):227-39. Epub 2009 Feb 13

Caspary DM, Ling L, Turner JG, Hughes LF.
Inhibitory neurotransmission, plasticity and aging in the mammalian central auditory system. J Exp Biol. 2008 Jun;211(Pt 11):1781-91. Pub Med Link >

Bauer CA, Turner JG, Caspary DM, Myers KS, Brozoski TJ.
Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma.J Neurosci Res. 2008 Apr 25. [Epub ahead of print] Pub Med LInk >

Schatteman TA, Hughes LF, Caspary DM. Aged-related loss of temporal processing: Altered responses to amplitude modulated tones in rat dorsal cochlear nucleus.
Neuroscience. 2008 Feb 29. [Epub ahead of print] Pub Med Link >

Brozoski, T.J., C.A. Bauer, D.M. Caspary: Elevated Fusiform Cell Activity in the Dorsal Cochlear Nucleus of Chinchillas with Psychophysical Evidence of Tinnitus. J. Neurosci. 22(6):2383-90, 2002.

Wang, J., S.L. McFadden, D.M. Caspary, R.J. Salvi: Gamma-Aminobutyric Acid Circuits Shape Response Properties of Auditory Cortex Neurons. Brain Res. 944:219-231, 2002.

Caspary, D.M., P.S. Palombi, L.F. Hughes: GABAergic Inputs Shape Responses to Sinusoidally Amplitude Modulated Stimuli in the Chinchilla Inferior Colliculus. Hearing Res. 168:163-173, 2002.

Turner, J.G., L.F. Hughes, D.M. Caspary: Divergent Response Properties of Layer V Neurons in Rat Primary Auditory Cortex. Hearing Res. 202:129-140, 2005.

Turner, J.G., J. Parrish, L.F. Hughes, L.A. Toth, D.M. Caspary: Hearing in Laboratory Animals: Strain Differences and Non-Auditory Effects of Noise. Comparative Medicine 55:12-23, 2005.

Ling, L.L., L.F. Hughes, D.M. Caspary: Age-Related Loss of the GABA Synthetic Enzyme in Rat Primary Auditory Cortex. Neurosci. 132:1103-1113, 2005.

Turner, J.G., L.F. Hughes, D.M. Caspary: Effects of Aging on Receptive Fields in Rat Primary Auditory Cortex Layer V Neurons. J. Neurophysiol.94:2738-2747, 2005.

Caspary, D.M., T.A. Schatteman, L.F. Hughes: Age-Related Loss of Response Inhibition in Rat Dorsal Cochlear Nucleus. J Neurosci. 23;25(47):10952-10959, 2005.

Brozoski, T.J., D.M. Caspary, C.A. Bauer: Marking multi-channel silicon-substrate electrode recording sites using radiofrequency lesions. J. Neurosci. Methods 150:185-191, 2006.

Turner, J.G., T.J. Brozoski, C.A. Bauer, J.L. Parrish, K. Myers, L.F. Hughes, D.M. Caspary: Rapid Tinnitus Screening in Rats Behavioral Neurosci. 120:188-195. 2006.

Caspary, D.M., L.F. Hughes, T.A. Schatteman, J.G. Turner: Age-Related Changes in the Response Properties of Cartwheel Cells in Rat Dorsal Cochlear Nucleus. Hearing Res. 214:on-line, 2006