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The Journal of Neuroscience, November 15, 2000, 20(22):8344-8353

Mismatched Appositions of Presynaptic and Postsynaptic Components in Isolated Hippocampal Neurons

Anuradha Rao, Eric M. Cha, and Ann Marie Craig

Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, and Department of Cell and Structural Biology, University of Illinois, Urbana, Illinois 61801

To determine whether presynaptic input is necessary for postsynaptic differentiation, we isolated hippocampal neurons in microisland culture and thus deprived pyramidal cells of GABA input and GABAergic neurons of glutamate input. We find that glutamate input is necessary for clustering the AMPA-type glutamate receptor but not for clustering the NMDA receptor or the associated PSD-95 family scaffold in GABAergic cells; GABA input is not necessary for clustering the GABAA receptor or gephyrin in pyramidal cells. Isolated neurons showed a surprising mismatch of presynaptic and postsynaptic components. For example, in isolated pyramidal neurons, although GABAA receptor clusters covered <4% of the dendritic surface and presynaptic boutons covered <12%, a full two-thirds of the GABAA receptor clusters were localized inappropriately opposite the non-GABAergic, presumed glutamatergic, terminals. Furthermore, inhibitory and excitatory postsynaptic components were segregated into separate clusters in isolated cells and apposed to separate boutons of a single axon. Thus, GABAA receptors were clustered opposite some terminals, whereas NMDA receptors were clustered opposite other terminals of a single axon. These results suggest the involvement of a synaptogenic signal common to glutamate and GABA synapses that permits experimentally induced mismatching of presynaptic and postsynaptic components in isolated neurons, as well as a second specificity-conferring signal that mediates appropriate matching in mixed cultures.

Key words: synaptogenesis; hippocampus; neuron culture; glutamate receptor; GABA receptor; PSD-95; gephyrin; autapse


Copyright © 2000 Society for Neuroscience  0270-6474/00/20228344-10$05.00/0


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