title: Evidence of key tinnitus-related brain regions documented by a unique combination of manganese-enhanced MRI and acoustic startle reflex testing.
abstract: Animal models continue to improve our understanding of tinnitus pathogenesis and aid in development of new treatments. However, there are no diagnostic biomarkers for tinnitus-related pathophysiology for use in awake, freely moving animals. To address this disparity, two complementary methods were combined to examine reliable tinnitus models (rats repeatedly administered salicylate or exposed to a single noise event): inhibition of acoustic startle and manganese-enhanced MRI. Salicylate-induced tinnitus resulted in wide spread supernormal manganese uptake compared to noise-induced tinnitus. Neither model demonstrated significant differences in the auditory cortex. Only in the dorsal cortex of the inferior colliculus (DCIC) did both models exhibit supernormal uptake. Therefore, abnormal membrane depolarization in the DCIC appears to be important in tinnitus-mediated activity. Our results provide the foundation for future studies correlating the severity and longevity of tinnitus with hearing loss and neuronal activity in specific brain regions and tools for evaluating treatment efficacy across paradigms.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America. agholt@med.wayne.edu
authors.forename: Avril Genene
authors.initials: AG
authors.lastname: Holt
authors.forename: David
authors.initials: D
authors.lastname: Bissig
authors.forename: Najab
authors.initials: N
authors.lastname: Mirza
authors.forename: Gary
authors.initials: G
authors.lastname: Rajah
authors.forename: Bruce
authors.initials: B
authors.lastname: Berkowitz
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D017626:Cochlear Nucleus; D004195:Disease Models, Animal; D007245:Inferior Colliculi / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012022:Reflex, Acoustic; D013216:Reflex, Startle; D020156:Salicylic Acid / Q000378:metabolism; D013997:Time Factors; D014012:Tinnitus / Q000175:diagnosis* / Q000503:physiopathology
chemical_list: D008345:Manganese; D020156:Salicylic Acid