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Activity-dependent modulation of synaptic AMPA receptor accumulation
R J O'Brien1, S Kamboj, M D Ehlers
1Howard Hughes Medical Institute, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Neuron
|December 18, 1998
Summary
Central neurons adjust excitatory synaptic input by regulating AMPA receptors. Inhibiting transmission increases synaptic AMPA receptors and mEPSC amplitudes, while increasing activity decreases them, indicating activity-dependent receptor turnover.
Area of Science:
- Neuroscience
- Cellular Neuroscience
- Synaptic Plasticity
Background:
- Central neurons exhibit homeostatic plasticity to maintain stable output despite fluctuating synaptic input.
- Understanding the mechanisms of synaptic scaling is crucial for comprehending neuronal network function.
Purpose of the Study:
- To investigate how excitatory synaptic transmission influences the number and function of AMPA receptors at synapses.
- To elucidate the role of AMPA receptor turnover in synaptic homeostasis.
Main Methods:
- Utilized cultured spinal neurons to study synaptic plasticity.
- Manipulated excitatory synaptic transmission to observe changes in AMPA receptor dynamics.
- Measured miniature excitatory postsynaptic current (mEPSC) amplitudes and AMPA receptor accumulation at synapses.
Main Results:
- Inhibition of excitatory transmission increased mEPSC amplitudes and synaptic AMPA receptor accumulation.
- Increased excitatory activity decreased synaptic AMPA receptors and mEPSC amplitudes.
- Synaptic remodeling occurred slowly, correlating with AMPA receptor metabolic half-life.
- Reduced transmission prolonged the half-life of the GluR1 AMPA receptor subunit.
Conclusions:
- Synaptic activity dynamically regulates the number of postsynaptic AMPA receptors.
- Neuronal activity modulates the size of mEPSCs by controlling AMPA receptor turnover.
- This provides a mechanism for synaptic homeostasis in central neurons.