Valproate Reduced Synaptic Activity Increase Induced by 4‐Aminopyridine at the Hippocampal CA3‐CA1 Synapse

Summary:  Purpose: We investigated the effects of valproate (VPA) on excitatory synaptic transmission changes induced by 4‐aminopyridine (4‐AP) to determine whether the antiepileptic effects shown by VPA can be ascribed to a modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in the CA3‐CA1 synapse. Methods: Rat hippocampal slices were prepared and maintained in vitro with standard methods. Whole‐cell current and voltage‐clamp recordings were obtained from CA1 pyramidal neurons by using the “blind” patch‐clamp technique in an immersion recording chamber. Increase in the spontaneous excitatory synaptic activity was induced by addition of 4‐AP to the medium. Results: Perfusion with VPA significantly counteracted the increase of frequency and amplitude of the sEPSCs induced by application of 4‐AP and suppressed the epileptiform activity. Conclusions: We conclude that VPA decreases the 4‐AP–induced enhancement of excitatory synaptic activity at the CA3‐CA1 synapse, and that this reduction of excitation input to CA1 contributes to the anticonvulsant effects of VPA.