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.
Isokawa
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Brain Research Institute, Center for the Health Sciences, University of California, Los Angeles 90024-1761.
Mello
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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