Clinical Professor, Molecular Medicine, CCLCM-CWRU
Location: Cleveland Clinic Main Campus
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.
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.
Gao Y, Manzoor N, Kaltenbach JA. (2016) Evidence of activity-dependent plasticity in the dorsal cochlear nucleus, in vivo, induced by brief sound exposure. Hear Res 341:31-42. PMID: 27490001; PMCID: PMC5086438
Salloum RH, Sandridge S, Patton DJ, Stillitano G, Dawson G, Niforatos J, Santiago L, Kaltenbach JA. (2016) Untangling the effects of tinnitus and hypersensitivity to sound (hyperacusis) in the gap detection test. Hear Res 331:92-100. PMID: 26520582
Salloum RH, Yurosko C, Santiago L, Sandridge SA, Kaltenbach JA. (2014) Induction of enhanced acoustic startle response by noise exposure: dependence on exposure conditions and testing parameters and possible relevance to hyperacusis. PLoS One 9(10):e111747. PMID: 25360877; PMCID: PMC4216136
Salloum RH, Chen G, Velet L, Manzoor NF, Elkin R, Kidd GJ, Coughlin J, Yurosko C, Bou-Anak S, Azadi S, Gohlsch S, Schneider H, Kaltenbach JA. (2014) Mapping and morphometric analysis of synapses and spines on fusiform cells in the dorsal cochlear nucleus. Front Syst Neurosci 8:167. PMID: 25294990; PMCID: PMC4172007
Park HJ, Bonmassar G, Kaltenbach JA, Machado AG, Manzoor NF, Gale JT. (2013) Activation of the central nervous system induced by micro-magnetic stimulation. Nat Commun 4:2463. PMID: 24030203; PMCID: PMC3845906
Manzoor NF, Chen G, Kaltenbach JA. (2013) Suppression of noise-induced hyperactivity in the dorsal cochlear nucleus following application of the cholinergic agonist, carbachol. Brain Res 1523:28-36. PMID: 23721928; PMCID: PMC3748938
Godfrey DA, Kaltenbach JA, Chen K, Ilyas O. (2013) Choline acetyltransferase activity in the hamster central auditory system and long-term effects of intense tone exposure. J Neurosci Res 91(7):987-96. PMID: 23605746; PMCID: PMC4469331
Chen G, Lee C, Sandridge SA, Butler HM, Manzoor NF, Kaltenbach JA. (2013) Behavioral evidence for possible simultaneous induction of hyperacusis and tinnitus following intense sound exposure. J Assoc Res Otolaryngol 14(3):413-24. PMID: 23440516; PMCID: PMC3642276
Manzoor NF, Gao Y, Licari F, Kaltenbach JA. (2013) Comparison and contrast of noise-induced hyperactivity in the dorsal cochlear nucleus and inferior colliculus. Hear Res 295:114-23. PMID: 22521905; PMCID: PMC3538909
Godfrey DA, Kaltenbach JA, Chen K, Ilyas O, Liu X, Licari F, Sacks J, McKnight D. (2012) Amino acid concentrations in the hamster central auditory system and long-term effects of intense tone exposure. J Neurosci Res 90(11):2214-24. PMID: 22715056; PMCID: PMC4470322
Manzoor NF, Licari FG, Klapchar M, Elkin RL, Gao Y, Chen G, Kaltenbach JA. (2012) Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus. J Neurophysiol 108(4):976-88. PMID: 22552192; PMCID: PMC3424082
Licari FG, Shkoukani M, Kaltenbach JA. Stimulus-dependent changes in optical responses of the dorsal cochlear nucleus using voltage-sensitive dye. J Neurophysiol 106(1):421-36. PMID: 21543759; PMCID: PMC3129723
Kaltenbach JA. (2011) Tinnitus: Models and mechanisms. Hear Res 276(1-2):52-60. PMID: 21146597; PMCID: PMC3109239
Roberts LE, Eggermont JJ, Caspary DM, Shore SE, Melcher JR, Kaltenbach JA. (2010) Ringing ears: the neuroscience of tinnitus. J Neurosci 30(45):14972-9. PMID: 21068300; PMCID: PMC3073522