title: GABAergic neural activity involved in salicylate-induced auditory cortex gain enhancement.
abstract: Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate (SS)-induced hyperexcitability and "increased central gain," we examined the effects of GABA receptor agonists and antagonists on SS-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of SS significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of SS also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the SS-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the SS-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the SS-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by SS may arise from a SS-induced suppression of GABAergic inhibition in the AC.
authors.affiliation: Center for Hearing and Deafness, Department of Communicative Disorders and Sciences, State University of New York at Buffalo, 3435 Main Street, NY 14214, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: E
authors.initials: E
authors.lastname: Lobarinas
authors.forename: A
authors.initials: A
authors.lastname: Deng
authors.forename: R
authors.initials: R
authors.lastname: Goodey
authors.forename: D
authors.initials: D
authors.lastname: Stolzberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Salvi
authors.forename: W
authors.initials: W
authors.lastname: Sun
mesh_terms: D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001303:Auditory Cortex / Q000187:drug effects* / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D020888:Vigabatrin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018682:GABA Agents; D005680:gamma-Aminobutyric Acid; D020888:Vigabatrin; D001418:Baclofen; D001241:Aspirin