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Mobile NMDA receptors at hippocampal synapses
Kenneth R Tovar1, Gary L Westbrook
1Vollum Institute, Oregon Health and Science University, Portland, OR 97201, USA.
Neuron
|April 24, 2002
Summary
Synaptic NMDA receptors are not fixed in place. New research shows these crucial glutamate receptors can move laterally into synapses, indicating a dynamic postsynaptic structure.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Glutamate receptors, particularly NMDA receptors, are key components of central synapses.
- The traditional view posits a stable postsynaptic membrane with anchored receptors.
- Recent findings suggest rapid receptor dynamics, challenging this stability model.
Purpose of the Study:
- To investigate the stability and dynamics of synaptic NMDA receptors in cultured hippocampal neurons.
- To determine if NMDA receptors are mobile within the postsynaptic complex.
Main Methods:
- Utilized open-channel blockers (+)-MK-801 and ketamine to tag synaptic NMDA receptors.
- Analyzed NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) recovery after blockade.
- Quantified receptor mobility based on recovery kinetics.
Main Results:
- Observed anomalous recovery of NMDA receptor-mediated EPSCs after MK-801 block.
- Ruled out MK-801 unbinding or new receptor insertion as causes for recovery.
- Demonstrated lateral movement of membrane receptors into the synapse, with at least 65% of synaptic NMDA receptors being mobile.
Conclusions:
- NMDA receptors exhibit lateral mobility, moving between synaptic and extrasynaptic locations.
- Provides evidence for a dynamic, rather than static, organization of NMDA receptors in the postsynaptic complex.
- Challenges the long-held view of rigidly anchored synaptic receptors.