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Volume 16, Number 23,
Issue of December 1, 1996
pp. 7496-7504
Copyright ©1996 Society for Neuroscience
Direct Measurement of AMPA Receptor Desensitization Induced by
Glutamatergic Synaptic Transmission
Received Aug. 2, 1996; revised Sept. 11, 1996; accepted Sept. 13, 1996.
Thomas Otis,
Su Zhang, and
Laurence O. Trussell
Department of Neurophysiology, University of Wisconsin, Madison,
Wisconsin 53706
Although almost all ionotropic neurotransmitter receptors undergo
desensitization, the onset and recovery of desensitization at a synapse
have never been observed directly. We have found changes in
postsynaptic AMPA receptor sensitivity in neurons of the chick cochlear
nucleus, the nucleus magnocellularis (nMAG), by photolysis of caged
glutamate immediately after activation of a single synaptic input.
Additionally, synaptic desensitization was demonstrated via competition
between synaptically released glutamate and an exogenous
nondesensitizing agonist, kainate. Both approaches indicated that at
least 35-40% of the receptors were desensitized after a single
synaptic stimulus. Miniature synaptic currents were depressed after an
evoked synaptic current, indicating that desensitization led to a
reduction in the response to individual transmitter quanta. Stimulation
of adjacent glutamatergic inputs to the same cell demonstrated that
nearby terminals did not depress one another, suggesting that the
desensitizing level of glutamate is restricted to each axon terminal.
These findings confirm that postsynaptic neurons may use
desensitization to regulate the strength of transmission on a
synapse-specific basis.
Key words:
glutamate receptors;
kainate;
AMPA;
desensitization;
synaptic transmission;
voltage clamp;
caged compounds;
auditory;
brain slice
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