Abstracts

Temporal lobe epilepsy has long been associated with cognitive impairment, but it remains unclear whether this is due to a shared cause, or that seizures impair normal information processing in networks through plastic changes. Intra-hippocampal tetanus toxin induces several weeks of spontaneous seizures and a permanent impairment of spatial learning. In this study we assessed whether tetanus toxin-induced seizures affect the gamma frequency band oscillations, associated with cortical information processing.
Chronic epilepsy was induced in 8 Sprague Dawley rats by injection of tetanus toxin in the left dorsal hippocampus. Behavioural seizures (partial and occasionally generalised) were scored using video monitoring. 7 controls received a saline injection. 2-3 weeks post-injection rats were sacrificed and 400 [mu]m slices were made from the ipsilateral ventral hippocampus and kept in an interface recording chamber. Field potentials were recorded from area CA3 stratum pyramidale. Recurrent excitation and recurrent inhibition in area CA3b were assessed by paired-pulse stimuli to the Schaffer collaterals. Gamma oscillations were induced by 100 nM kainate and assessed after 90 minutes.
Recurrent excitation (late population synaptic potential normalised to antidromic population spike) recurrent excitability (recurrent population spike normalised to population synaptic potential) and inhibition (recurrent population spike excitability ratio) were not different between slices from toxin-injected rats and saline-injected rats. The dominant frequency of kainate-induced oscillations was 34 Hz. The dominant gamma power (summated power at the dominant frequency [plusmn] 8 Hz) was maximal in CA3c, 25% in CA3b and 4% in CA3a. In slices from toxin-injected rats gamma power was reduced by 70% in CA3c ([italic]P[/italic][lt]0.05), by 82% in CA3b ([italic]P[/italic][lt]0.01) and by 54% in CA3a ([italic]P[/italic][lt]0.05). The dominant frequency and auto-correlation for each area and the cross-correlation between area[apos]s CA3c and CA3b or CA3a were not different.
The power of [italic]in vitro[/italic] induced gamma oscillation power was strongly reduced in the ventral hippocampus of epileptic rats, without affecting frequency or coherence. This may contribute to learning difficulties observed in tetanus toxin-induced epilepsy. As local excitability was unaffected, this may be caused by a reduced kainate receptor-mediated drive. The expression of the kainate receptor subunit GluR6, required for kainate-induced gamma, is reduced in tissue resected from temporal lobe epilepsy patients and is currently assessed in hippocampal tissue from rats used in this study.
[Supported by: The Wellcome Trust]