Abstract
Membrane properties and synaptic responses were analyzed in dentate granule cells in hippocampal slices prepared from pilocarpine-treated, chronically epileptic rats. Perforant path stimulation evoked a long-lasting excitatory postsynaptic potential (EPSP) with multiple spikes in a stimulus intensity-dependent fashion. The response was strongly facilitated by paired-pulse stimulation. Application of N- methyl- d-aspartate (NMDA) receptor antagonist, d-2-amino-5-phosphonovalerate (APV), not only blocked the paired pulse facilitation but also reduced the amplitude of the EPSP, indicating the involvement of the NMDA-receptor in synaptic responses of pilocarpine-treated dentate granule cells. Dendrites of these neurons showed loss of spines and beaded branches. These findings suggest that a degenerating dendrite could be a morphological substrate of neuronal hyperexcitability mediated by NMDA receptors, implicating possible in vivo glutamate toxicity as an underlying mechanism of chronic epilepsy.
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