Role of GABA abnormalities in the inferior colliculus pathophysiology - audiogenic seizures.
gamma-Aminobutyric acid (GABA), acting at GABA(A) receptors, mediates inhibition in inferior colliculus (IC) central nucleus (ICc) neurons and plays a prominent role in mediating acoustically evoked non-monotonicity, offset inhibition, and binaural inhibition, and is also important in tonic inhibition. The IC plays an important role in a number of pathophysiological conditions that involve hearing, including tinnitus, age-related hearing loss, and audiogenic seizures (AGS). AGS are a major form of rodent neurological disorder that can be genetically mediated and can also be readily induced in both young and mature animals. A deficit in GABA-mediated inhibition in IC neurons has been shown to be a critical mechanism in genetic and induced forms of AGS. Thus, both endogenously evoked GABA-mediated inhibition and exogenously applied GABA are reduced in efficacy in IC neurons of rats that are susceptible to AGS. GABA-mediated inhibition in IC neurons is significantly more easily blocked by a GABA(A) antagonist in genetic and induced forms of AGS in vivo and in vitro. AGS can be induced in normal animals by treatments that reduce the effectiveness of GABA in the IC. Glutamate-mediated excitation is a critical element of neurotransmission in IC neurons, and excessive activation of glutamate receptors in the IC is also strongly implicated as the other major mechanism in the pathophysiology of AGS. These neurotransmitter abnormalities result in excessive firing of ICc neurons that acts as the critical initiation mechanism for triggering seizures in response to intense acoustic stimuli.
Faingold
Carl L
CL
Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, USA. cfaingold@siumed.edu
D000161:Acoustic Stimulation; D020270:Alcohol Withdrawal Seizures / Q000503:physiopathology; D000818:Animals; D020195:Epilepsy, Reflex / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology; D007245:Inferior Colliculi / Q000503:physiopathology*; D051379:Mice; D009415:Nerve Net / Q000503:physiopathology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018756:GABA Antagonists; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid