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 Honors and Awards

Chair: American Institute of Biological Sciences DOD Study section

Member: Tinnitus Research Consortium Board of Directors and Scientific Review Panel

Member: American Tinnitus Association Scientific Review Panel

Recent Publications:

Wang H., Brozoski TJ, Ling L, Hughes LF,^ and Caspary DM:^ Impact of Sound Exposure and Aging on Brain Derived Neurotrophic Factor and TrkB Receptor Levels in Dorsal Cochlear Nucleus 80 Days Following Sound Exposure. Neurosci.  Jan 13;172:453-9, 2011 PMID: 21034795

Richardson BD, Ling LL, Uteshev VV, and Caspary DM: Extrasynaptic GABA_A receptors and tonic inhibition in rat auditory thalamus. PLoS One. 2011 Jan 26;6(1):e16508. PMID: 21298071

Richardson BD, Ling LL, Uteshev VV, and Caspary DM.  Aged-Related Changes in GABAARs in the Medial Geniculate Body. Soc. Neurosci. Abstr. 41:476.02, 2011

Recent Presentations/Invited Talks

Caspary, D.M. Invited Speaker. Association for Research in Otolaryngology- Symposium entitled: Presbycusis: From Animal Models to Human Perceptual Deficits.  February 2011.