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This Article Full Text Full Text (PDF) All Versions of this Article: 102/1/578    most recent 91342.2008v2 91342.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Li, Y. Articles by Liu, G. PubMed PubMed Citation Articles by Li, Y. Articles by Liu, G.

Glycine Site of NMDA Receptor Serves as a Spatiotemporal Detector of Synaptic Activity Patterns

¹Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts; ²Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts; and ³Center for Learning and Memory, School of Medicine, Tsinghua University, Beijing, China

Submitted 19 December 2008; accepted in final form 8 May 2009

Calcium influx associated with the opening of N-methyl-D-aspartate (NMDA) receptor channels is the major signal triggering synaptic and developmental plasticity. Controlling the NMDA receptor function is therefore critical for many functions of the brain. We explored the mechanisms of synaptic activation of the NMDAR glycine site by endogenous coagonist using whole cell voltage-clamp recordings from hippocampal neurons in mixed cultures, containing both neurons and glial cells, and, under more physiological conditions, in hippocampal slices. Here we show that the glycine site of the NMDA receptor at hippocampal synapses, both in culture and acute brain slices, is not saturated by the ambient coagonist concentration and is modulated through activity-dependent coagonist release. Augmentation of the NMDA receptor-mediated synaptic responses by local glutamate-induced coagonist release is spatially restricted and determined by spatiotemporal summation of synaptic events at neighboring synaptic inputs on a single dendritic branch. Therefore different spatiotemporal patterns of presynaptic activity could be translated into different levels of the NMDAR activation in specific afferent projections. These results suggest that the NMDA receptor glycine site may serve as a detector of the spatiotemporal characteristics of presynaptic activity patterns.