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Publication : NMDA receptors regulate developmental gap junction uncoupling via CREB signaling.

First Author  Arumugam H Year  2005
Journal  Nat Neurosci Volume  8
Issue  12 Pages  1720-6
PubMed ID  16299502 Mgi Jnum  J:103934
Mgi Id  MGI:3610881 Doi  10.1038/nn1588
Citation  Arumugam H, et al. (2005) NMDA receptors regulate developmental gap junction uncoupling via CREB signaling. Nat Neurosci 8(12):1720-6
abstractText  Signaling through gap junctions (electrical synapses) is important in the development of the mammalian central nervous system. Abundant between neurons during postnatal development, gap junction coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. Here we report that developmental uncoupling of gap junctions in the rat hypothalamus in vivo and in vitro is associated with a decrease in connexin 36 (Cx36) protein expression. Both developmental gap junction uncoupling and Cx36 downregulation are prevented by the blockade of NMDA glutamate receptors, action potentials and the calcium-cyclic AMP response element binding protein (CREB), and are accelerated by CREB overexpression. Developmental gap junction uncoupling and Cx36 downregulation are not affected by blockade of non-NMDA glutamate receptors, and do not occur in hypothalamic neurons from NMDA receptor subunit 1 (NMDAR1) knockout mice. These results demonstrate that NMDA receptor activity contributes to the developmental uncoupling of gap junctions via CREB-dependent downregulation of Cx36.
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