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The Journal of Neuroscience, 0000, 20:RC115:1-5

RAPID COMMUNICATION
The Dynamic Range for Gain Control of NMDA Receptor-Mediated Synaptic Transmission at a Single Synapse

Lu-Yang Wang

The Program for Brain and Behavioral Research and Division of Neurology, The Hospital for Sick Children and Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5G, 1X8

Although the level at which NMDA receptors (NMDARs) are activated can profoundly influence the direction and extent of long-term changes in synaptic strength, the probabilistic nature of quantal release at individual synapses makes it difficult to determine the dynamic operating range of NMDAR-mediated synaptic transmission. By continually driving glutamate release from a single high-fidelity auditory synapse with bursts of high-frequency stimuli, I show here that NMDAR-mediated EPSCs exhibited incremental summation in their amplitude and did not reach a plateau until six or seven consecutive stimuli into the train. An increase in the initial quantal output, by broadening presynaptic spikes with the potassium channel blocker tetraethylammonium (TEA, 0.2 mM), slightly increased the plateau amplitude at 200/300 Hz but shifted its peak temporally toward the earlier stimuli. These results suggest that the plateau amplitude in TEA reflects the activation of the entire population of synaptic NMDARs and hence the maximal gain of NMDAR-mediated synaptic transmission. This maximum was estimated to be 3.2-fold of the basal synaptic strength, giving a 31% occupancy of synaptic NMDARs by glutamate. Thus, synaptic NMDARs possess a broad dynamic range within which the activity-dependent control of synaptic strength and plasticity can potentially be tuned by the amount of Ca²⁺ influx associated with different levels of NMDAR occupancy within the same synapse.

Key words: calyx of Held-MNTB synapse; Ca²⁺; glutamate release; synaptic NMDA and AMPA receptors; gain range; synaptic plasticity

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

This article has been cited by other articles:

				I. Joshi, Y.-M. Yang, and L.-Y. Wang Coincident Activation of Metabotropic Glutamate Receptors and NMDA Receptors (NMDARs) Downregulates Perisynaptic/Extrasynaptic NMDARs and Enhances High-Fidelity Neurotransmission at the Developing Calyx of Held Synapse J. Neurosci., September 12, 2007; 27(37): 9989 - 9999. [Abstract] [Full Text] [PDF]

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