GABAergic neural activity involved in salicylate-induced auditory cortex gain enhancement.
Lu J, Lobarinas E, Deng A, Goodey R, Stolzberg D, Salvi RJ, Sun W.
Center for Hearing and Deafness, State University of New York at Buffalo, 3435 Main Street, NY 14214, USA.
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.
Fuente: Neuroscience. 2011 Aug 25;189:187-98. Epub 2011 Jun 12.