AGE-RELATED EPILEPTOGENIC EFFECTS OF CORTICOTROPIN-RELEASING HORMONE IN THE ISOLATED CA1 REGION OF RAT HIPPOCAMPAL SLICES

1. The effects of corticotropin-releasing hormone (CRH) on synapticall y evoked population and intracellular responses in the isolated rat CA 1 region of hippocampal slices were studied to evaluate possible diffe rences between adult and juvenile rats. 2. The amplitude of orthodromi cally evoked (stratum radiatum stimulation) population spikes was reve rsibly enhanced by 0.2-0.6 mu M CRH to a greater extent in slices from juvenile rats than from adult rats. In no case, however, did CRH caus e seizurelike activity to develop under normal recording conditions. 3 . In the presence of 10-30 mu M bicuculline, interictal-like bursts of population spikes and corresponding intracellularly recorded action p otentials could be evoked starting at postnatal day 8. The number of s pikes and the duration of the evoked bursts in the CA1 region were rev ersibly increased by CRH (0.2-0.6 mu M) to a greater extent in slices from juvenile than from adult rats. 4. The amplitude of the afterhyper polarization following intracellularly evoked bursts of action potenti als in CA1 pyramidal cells was reduced by 0.2 mu M CRH to a Similar de gree in both young and adult rats. No consistent changes in input resi stance or membrane potential were observed. 5. No correlation was foun d between the magnitude of the CRH-induced increase in responsiveness and the initial excitability in controls, suggesting that the CRH-indu ced changes were independent of any age-dependent differences in gener al slice excitability. 6. Our results indicate that, in the CA1 region , CRH augments bicuculline-induced bursts to a greater extent in slice s from young versus adult rats. These findings support the hypothesis that CRH may be involved in the development of massive infantile spasm s, a form of childhood epilepsy. However, CRH probably does not initia te seizurelike activity by acting solely in the hippocampus.