NMDA receptor-mediated excitability in dendritically deformed dentate granule cells in pilocarpine-treated rats.
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.
Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles 90024-1761.
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Isokawa
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Mello
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D003712:Dendrites / Q000502:physiology*; D004827:Epilepsy / Q000209:etiology; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate