The focus of research in my laboratory is on the role of neural plasticity in the pathogenesis of hearing disorders, especially those caused by excessive noise and ototoxic drug exposure. Injury to the ear caused by these insults triggers plastic readjustments in the central auditory pathways of the brain, inducing neurons into an abnormal state of hyperactivation. Their levels of firing in silence as well as their responses to sound stimuli become exaggerated, leading to altered sound perception.
Two auditory disorders that are hypothesized to stem from this hyperactive state include tinnitus and hyperacusis. Tinnitus is a condition in which people perceive an ongoing troubling sound in the absence of a driving acoustic input. Approximately 2-3 million Americans suffer from a severe, disabling form of tinnitus, and a large proportion of these individual also suffer from hyperacusis, characterized by exaggerated sense of loudness in response to sound stimuli.
We are presently studying the mechanisms that underlie this hyperactive state. We have localized the cellular generators of hyperactivity to auditory brainstem nuclei and have shown that this hyperactivity is correlated with the percepts of tinnitus and hyperacusis measured behaviorally. We now seek to link these changes to precise alterations in the cartography and ultrastructure of synaptic inputs to hyperactive neurons, and to changes in receptor sensitivity to neuromodulators implicated in the control of cellular excitability. These are viewed as steps that are critical to the improvement of treatment for these disturbing disorders.
Kaltenbach, J.A., Rachel, et al. (2002) Cisplatin-induced hyperactivity in the dorsal cochlear nucleus and its relations to outer hair cell loss: Implications for an understanding of tinnitus. J. Neurophysiol. 88: 699-714.
Godfrey, D.A. Mikesell, Kaltenbach, J.A. et al. (2008) Effects of high-intensity sound exposure on neurotransmitter chemistry in the central auditory system. Seminars in Hearing 29: 259-269.
Finlayson, P. and Kaltenbach, J.A. (2009) Alterations in the spontaneous discharge patterns of single units in the dorsal cochlear nucleus following Intense sound exposure. Hearing Res. (Epub).
Lerner Research Institute
Mail Code NB21
9500 Euclid Avenue
Cleveland, Ohio 44195