Loss of intensity-induced inhibition in inferior colliculus neurons leads to audiogenic seizure susceptibility in behaving genetically epilepsy-prone rats.
The genetically epilepsy-prone rat (GEPR) exhibits elevated seizure sensitivity and audiogenic seizures (AGS). The inferior colliculus (IC) is the most critical brain region for AGS initiation. The present study evaluated IC neuronal firing and convulsive behavior simultaneously in freely moving GEPRs. High intensity acoustic stimulation produces neuronal firing reductions (intensity-induced inhibition) in about 50% of IC neurons in normal rats. However, in GEPR IC neurons, intensity-induced inhibition is significantly less effective than normal. Offset inhibition is also reduced in GEPR IC neurons, which leads to a greater than normal incidence of offset (afterdischarge) responses at high stimulus intensities. At AGS onset most IC neurons exhibit burst firing and reductions of acoustically evoked neuronal responses. Responsiveness to acoustic stimuli returns following AGS. This change in IC neuronal firing pattern suggests that the network that governs IC neuronal firing has temporarily changed from the auditory system to the network that mediates seizure propagation. GABA is strongly implicated in intensity-induced, binaural, and offset inhibition in IC neurons. The diminished efficacy of these forms of GABA-mediated acoustically evoked inhibition in the GEPR IC extends previous results, showing reduced effectiveness of exogenously applied GABA and benzodiazepine in GEPR IC neurons. This reduced effectiveness of GABA-mediated inhibition along with excess excitant amino acids in GEPR IC, previously reported, appear to be vital neurotransmitter mechanisms, subserving the exaggerated output of IC neurons at high acoustic intensities. This exaggerated IC firing may be instrumental in seizure initiation in this epilepsy model.
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794.
C L
CL
Faingold
C A
CA
Anderson
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal; D004198:Disease Susceptibility; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D007245:Inferior Colliculi / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000209:etiology / Q000503:physiopathology*