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A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
Recruiting extrasynaptic NMDA receptors augments synaptic signaling
Alexander Z Harris1, Diana L Pettit
1Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Journal of Neurophysiology
|December 7, 2007
Summary
Extrasynaptic N-Methyl-D-aspartate receptors (NMDARs) are activated by stimulation frequencies as low as 25 Hz, participating in synaptic transmission. These receptors play a vital role in synaptic physiology, challenging their "extrasynaptic" classification.
Area of Science:
- Neuroscience
- Cellular Biology
- Synaptic Plasticity
Background:
- N-Methyl-D-aspartate receptors (NMDARs) have dual roles in cell survival and death, contingent on synaptic versus extrasynaptic activation.
- Differential NMDAR activation is hypothesized to regulate synaptic plasticity direction.
Purpose of the Study:
- To determine the physiological parameters required for activating extrasynaptic NMDARs in brain slices.
- To investigate the role of extrasynaptic NMDARs in synaptic transmission and plasticity.
Main Methods:
- Utilized the irreversible NMDAR antagonist MK-801 to selectively isolate extrasynaptic NMDARs.
- Tested stimulation trains ranging from 5 to 400 Hz on CA1 hippocampal slice pyramidal neurons.
Main Results:
- Extrasynaptic NMDARs were engaged by frequencies as low as 25 Hz, with peak activation between 100 and 200 Hz.
- 175 Hz stimulation activated both synaptic and extrasynaptic NMDARs, indicating their participation in synaptic transmission.
- Results suggest extrasynaptic NMDARs function as synaptic receptors when needed, enhancing synaptic strength.
Conclusions:
- Extrasynaptic NMDARs are regularly involved in synaptic transmission, particularly during bursts of activity.
- The findings challenge the traditional classification of these receptors as solely
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