Audiogenic kindling increases neuronal responses to acoustic stimuli in neurons of the medial geniculate body of the genetically epilepsy-prone rat.
Frequent repetition of audiogenic seizure (AGS) ('AGS kindling') in the severe substrain of genetically epilepsy-prone rats (GEPR-9s) results in the appearance of cortical epileptiform electrographic activity, increases of seizure duration and additional convulsive behaviors. These findings suggest that the initial AGS network, which is located primarily in the brainstem, has undergone expansion to the forebrain. The medial geniculate body (MGB) is a thalamic structure that is the first major auditory nucleus efferent to the AGS-initiating site in the inferior colliculus. The MGB is not required for AGS induction, but it has been implicated in the expanded AGS network in GEPR-9s based on focal, pharmacological blockade experiments. The present study examined changes in acoustically evoked MGB neuronal responses in awake and behaving GEPR-9s and in anesthetized GEPR-9s after 14 repetitive AGS-inducing stimuli given daily. An elevated number of action potentials was observed in the MGB neuronal responses after AGS kindling in GEPR-9s. This increase of MGB neuronal responses was associated with a loss of habituation and lasted for at least 28 days after the 14th AGS. An increase in the incidence of sustained acoustic responses in MGB neurons was observed after repetitive AGS in GEPR-9s. Increases in the peak latency and threshold of MGB neuronal responses were also observed after AGS kindling. MGB neurons exhibited a rapid tonic firing during tonic seizures in behaving GEPR-9s, suggesting that the MGB may be implicated in the propagation of seizure activity. However, MGB neuronal firing was silent during post-tonic clonus, a behavior seen in GEPR-9s only after AGS repetition, suggesting that MGB does not play a direct role in the generation of this convulsive behavior. Thus, changes in neuronal firing in nuclei efferent to the MGB, in the expanded neuronal network for repetitive AGS, may be responsible for the generation of post-tonic clonus in GEPR-9s.
N'Gouemo
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Department of Pharmacology, Southern Illinois University School of Medicine, Springfield 62794-1222, USA.
Faingold
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CL
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004594:Electrophysiology; D004827:Epilepsy / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005829:Geniculate Bodies / Q000166:cytology*; D007696:Kindling, Neurologic / Q000502:physiology*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000502:physiology