Inferior colliculus neuronal response abnormalities in genetically epilepsy-prone rats: evidence for a deficit of inhibition.
The genetically epilepsy-prone rat (GEPR) is abnormally susceptible to induction of seizures by acoustic stimulation. The inferior colliculus (IC) is critically important to audiogenic seizure susceptibility. The GEPR is more susceptible to induction of audiogenic seizures at 12 kHz than at other pure tone frequencies. IC neurons in the GEPR exhibit significantly elevated response thresholds and broader tuning characteristics than normal. These findings along with previous neurophysiological and anatomical data suggest that a hearing deficit occurs in the GEPR. IC neurons in the GEPR exhibit a significantly elevated incidence of a response pattern with a peak of activity at the beginning and end of the stimulus, the onset-offset response. This response pattern occurs at 12 kHz and at characteristic frequency with high stimulus intensities and may represent an afterdischarge phenomenon. The onset-offset pattern may be a manifestation of central mechanisms developed to compensate for reduced peripheral auditory input that appears to be involved in the hearing deficit of the GEPR. Such compensatory mechanisms may involve alterations of the actions of neurotransmitters of the brain-stem auditory nuclei. GABA is implicated as an inhibitory transmitter in the IC. Iontophoretic application of GABA or a benzodiazepine produces significantly less inhibition of IC neurons of the GEPR than of the normal rat. Endogenous sound-induced (binaural) inhibition which is suggested to be GABA-mediated is also significantly reduced in IC neurons of the GEPR. Iontophoresis of the GABAA antagonist, bicuculline, often converts normal response patterns in the IC to onset-offset responses seen with high incidence in GEPR IC neurons, suggesting that the decreased effectiveness of GABA may lead to the onset-offset prevalence. This reduced effectiveness of inhibition may be unable to compensate for the rise in the putative excitatory transmitter, aspartate, in IC during high intensity acoustic stimulation in the GEPR. These altered transmitter actions may be important mechanisms subserving initiation of audiogenic seizures in the genetically epilepsy-prone rat.
D000161:Acoustic Stimulation; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D007245:Inferior Colliculi / Q000187:drug effects / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D001640:Bicuculline