Abstracts

Rationale: Estrogens differentially regulate neuronal excitability, synaptic plasticity, as well as biphasically modulate seizure activity: Some types of seizures may be exacerbated while other types are rather attenuated by estrogens. The mechanisms involved in these distinct effects of estrogens on seizure activity are unknown. Here we examined a form of synaptic plasticity in the dentate gyrus that may share some mechanisms with seizures. The dentate gyrus is a part of hippocampal formation and receives its main inputs from the entorhinal cortex via the perforant pathway; it serves as a gate and filters incoming information and seizure activity into the hippocampus. Previously we have reported that administration of beta-estradiol (EB) in ovariectomized (OVX) rats persistently enhances inhibition of dentate granule cells by selectively filtering out incoming low-frequency (3-5 Hz) but not the high-frequency activities. Using long-term potentiation (LTP) we investigated the effects of EB on synaptic plasticity in the dentate gyrus using different frequency induction paradigms. Methods: Adult female Sprague - Dawley rats were OVX and following one week treated subcutaneously with EB (2 ?g/0.1 ml) or oil (0.1 ml) daily for 4 days. Transversal slices containing the entorhinal cortex-hippocampus were prepared for extracellular recording. Our LTP induction paradigms involved (1) A theta burst stimulation (TBS), (2) Standard high-frequency stimulation (sHFS) and (3) Repeated high-frequency stimulation (rHFS). Results: In slices from EB-treated rats, the TBS of medial perforant pathway elicited smaller LTP compared to slices from oil-injected OVX controls. On the other hand, rHFS of medial perforant pathway in slices from EB-treated rats induced more robust LTP than that in oil-injected OVX controls. The magnitude of LTP induced by sHFS of medial perforant pathway didn t differ between EB and oil treated rats. Conclusions: Our data suggest that the anticonvulsant or proconvulsant effects of beta-estradiol in epileptic patients may depend on frequencies involved in seizure activity in distinct types of epilepsy. Supported by grants: NS 056093, NS 059504, and NS-20253 from NINDS.