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The Journal of Neuroscience, August 15, 2001, 21(16):6387-6394

Group I Metabotropic Glutamate Receptors Elicit Epileptiform Discharges in the Hippocampus through PLCbeta 1 Signaling

Shih-Chieh Chuang1, Riccardo Bianchi1, Daesoo Kim2, Hee-Sup Shin2, and Robert K. S. Wong1

1 Department of Physiology and Pharmacology, State University of New York-Health Science Center at Brooklyn, Brooklyn, New York 11203, and 2 National CRI Center for Calcium and Learning, Department of Life Science, Pohang University of Science and Technology, Pohang, 790-784, Korea

Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neurons and attempted to determine their role in the generation of the network activities. Group I mGluR stimulation causes depolarization of hippocampal neurons. This depolarization is primarily mediated by two sets of conductance change: the opening of a voltage-dependent cationic conductance (mediating ImGluR(V)) and the closing of a voltage-independent (background) K+ conductance. ImGluR(V) was no longer elicited by group I mGluR agonists in the presence of U73122, a phospholipase C (PLC) blocker. Also, the current could not be activated in hippocampal CA3 neurons from PLCbeta 1 knock-out mice. In contrast, suppression of PLC signaling did not affect the group I mGluR-mediated suppression of background K+ conductance. Thus, the suppression of the background K+ conductance occurred upstream to PLC activation, whereas the generation of ImGluR(V) occurred downstream to PLC activation. Group I mGluR agonists normally elicited rhythmic single cell and population burst responses in the CA3 neurons. In the absence of an ImGluR(V) response, CA3 neurons in slices prepared from PLCbeta 1-/- mutant mice could no longer generate these responses. The results suggest that ImGluR(V) expression in CA3 hippocampal neuron is PLCbeta 1-dependent and that ImGluR(V) plays a necessary role in the generation of rhythmic single cell bursts and synchronized epileptiform discharges in the CA3 region of the hippocampus.

Key words: PLCbeta 1; signal transduction; epileptiform discharges; mGluRs; hippocampus; CA3 population oscillations


Copyright © 2001 Society for Neuroscience  0270-6474/01/21166387-08$05.00/0


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