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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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