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Immunogold electron microscopic evidence of differential regulation of GluN1, GluN2A, and GluN2B, NMDA‐type glutamate receptor subunits in rat hippocampal CA1 synapses during benzodiazepine withdrawal
Author(s) -
Das Paromita,
Zerda Ricardo,
Alvarez Francisco J.,
Tietz Elizabeth I.
Publication year - 2010
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.22458
Subject(s) - ampa receptor , immunogold labelling , postsynaptic density , nmda receptor , glutamate receptor , biology , postsynaptic potential , hippocampal formation , long term potentiation , neuroscience , immunolabeling , glutamatergic , excitatory postsynaptic potential , biophysics , receptor , biochemistry , anatomy , ultrastructure , immunology , inhibitory postsynaptic potential , immunohistochemistry
Benzodiazepine withdrawal‐anxiety is associated with enhanced α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid receptor (AMPAR)‐mediated glutamatergic transmission in rat hippocampal CA1 synapses due to enhanced synaptic insertion and phosphorylation of GluA1 homomers. Interestingly, attenuation of withdrawal‐anxiety is associated with a reduction in N‐methyl‐D‐aspartate receptor (NMDAR)‐mediated currents and subunit expression, secondary to AMPA receptor potentiation. Therefore, in this study ultrastructural evidence for possible reductions in NMDAR GluN1, GluN2A, and GluN2B subunits was sought at CA1 stratum radiatum synapses in proximal dendrites using postembedding immunogold labeling of tissues from rats withdrawn for 2 days from 1‐week daily oral administration of the benzodiazepine, flurazepam (FZP). GluN1‐immunogold density and the percentage of immunopositive synapses were significantly decreased in tissues from FZP‐withdrawn rats. Similar decreases were observed for GluN2B subunits; however, the relative lateral distribution of GluN2B‐immunolabeling within the postsynaptic density did not change after BZ withdrawal. In contrast to the GluN2B subunit, the percentage of synapses labeled with the GluN2A subunit antibody and the density of immunogold labeling for this subunit was unchanged. The spatial localization of immunogold particles associated with each NMDAR subunit was consistent with a predominantly postsynaptic localization. The data therefore provide direct evidence for reduced synaptic GluN1/GluN2B receptors and preservation of GluN1/GluN2A receptors in the CA1 stratum radiatum region during BZ withdrawal. Based on collective findings in this benzodiazepine withdrawal‐anxiety model, we propose a functional model illustrating the changes in glutamate receptor populations at excitatory synapses during benzodiazepine withdrawal. J. Comp. Neurol. 518:4311–4328, 2010. © 2010 Wiley‐Liss, Inc.

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