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Developmental decrease in NMDA receptor desensitization associated with shift to synapse and interaction with

Bo Li1, Yo Otsu, Timothy H Murphy

  • 1Kinsmen Laboratory, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|December 6, 2003
PubMed
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During neuronal development, N-methyl-D-aspartate receptor (NMDAR) desensitization decreases. Synaptic localization and interaction with postsynaptic density-95 (PSD-95) stabilize NMDAR function in mature neurons.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • N-methyl-D-aspartate receptors (NMDARs) are critical for neuronal development and plasticity.
  • NMDAR function regulation is vital for physiological and pathological conditions.
  • Developmental changes in NMDAR subunit composition affect synaptic current decay rates.

Purpose of the Study:

  • To investigate developmental changes in NMDAR desensitization.
  • To determine the mechanisms underlying altered NMDAR desensitization during neuronal development.

Main Methods:

  • Whole-cell recording of NMDA-evoked currents in cultured rat hippocampal neurons.
  • Investigated the role of subunit composition, agonist sensitivity, and ion effects on desensitization.
  • Examined the impact of postsynaptic density-95 (PSD-95) interaction and synaptic localization on NMDAR desensitization.

Related Experiment Videos

Main Results:

  • Glycine-independent NMDAR desensitization decreases during neuronal development.
  • This developmental decrease is not linked to subunit composition or receptor sensitivity changes.
  • NMDAR desensitization correlates with synaptic localization and PSD-95 association.

Conclusions:

  • Synaptic localization and PSD-95 interaction stabilize NMDAR responses to sustained agonist exposure.
  • This mechanism differentially regulates NMDAR function across developmental stages.
  • Findings elucidate a novel mechanism for NMDAR regulation in neuronal development and plasticity.