Non-ionotropic signaling by the NMDA receptor: controversy and opportunity.
Provocative emerging evidence suggests that the N-methyl-d-aspartate (NMDA) receptor can signal in the absence of ion flux through the receptor. This non-ionotropic signaling is thought to be due to agonist-induced conformational changes in the receptor, independently of channel opening. Non-ionotropic NMDA receptor signaling has been proposed to be sufficient to induce synaptic long-term depression (LTD), directly challenging the decades-old model that prolonged low-level calcium influx is required to induce LTD. Here, we briefly review these recent findings, focusing primarily on the potential role of non-ionotropic signaling in NMDA receptor-mediated LTD. Further reports concerning additional roles of non-ionotropic NMDA receptor signaling are also discussed. If validated, this new view of NMDA receptor-mediated signaling will usher in an exciting new era of exploring synapse function and dysfunction.
Center for Neuroscience, University of California, Davis, CA, USA; Department of Neurology, University of California, Davis, CA, USA.
John A
JA
Gray
Center for Neuroscience, University of California, Davis, CA, USA; Department of Neurobiology, Physiology & Behavior, University of California, Davis, CA, USA.
Karen
K
Zito
Department of Pharmacology, University of California, Davis, CA, USA.
Johannes W
JW
Hell
LTD; NMDA; Non-ionotropic; signaling