Harsha Arumugam | PubMed Health

PubMed2005

NMDA receptors regulate developmental gap junction uncoupling via CREB signaling.

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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PubMed2004

Non-cholinergic excitation in neurons after a chronic glutamate receptor blockade.

Previous experiments revealed a dramatic increase in excitatory acetylcholine transmission in hypothalamic cultures during a chronic decrease in glutamate activity. Data suggested that in the absence of glutamate excitation, acetylcholine becomes the major excitatory neurotransmitter. However, non-cholinergic excitatory activity was also detected in some neurons. Here, using calcium imaging in hypothalamic cultures chronically subjected to the glutamate receptor blockade, we demonstrate the contribution of metabotropic glutamate receptors, P2-purinoreceptors, histamine receptors, adrenoreceptors, and gap junctions, but not nitric oxide to this non-cholinergic excitation. We also show that the sensitivity of neurons to receptor agonists is increased following the blockade. Data suggest that multiple components contribute to the excitatory activity in hypothalamic neurons during a long-term decrease in glutamate activity.

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