Journal of Neuroscience, Vol 11, 2947-2957, Copyright © 1991 by Society for Neuroscience
Chronic application of NMDA decreases the NMDA sensitivity of the evoked tectal potential in the frog
EA Debski, HT Cline, JW McDonald and M Constantine-Paton
Department of Neuroscience, University of Michigan, Ann Arbor 48109.
The activity-dependent mechanism that refines the topography of the
retinotectal projection in frogs is mediated by the NMDA receptor. Earlier
studies found that chronic treatment of the optic tectum with the NMDA
receptor antagonist DL-2-amino-5-phosphonovaleric acid (DL- AP5)
desegregated eye-specific stripes in three-eyed frogs, while chronic
treatment with NMDA sharpened stripe borders (Cline et al., 1987; Cline and
Constantine-Paton, 1990). We now report that this same chronic treatment
with NMDA decreases the electro-physiologically measured sensitivity of the
optic tectum to applied NMDA: acute application of a given concentration of
NMDA decreased the evoked tectal potential to a lesser extent in animals
chronically treated with NMDA than it did in normal and sham-treated
animals. This is observed as a shift to the right in the NMDA dose-response
curves for both the positive and negative postsynaptic components of the
evoked tectal response. We believe that this decreased NMDA receptor
effectiveness further restricts the intermingling of axon branches from the
two eyes by limiting synapse stabilization to areas where afferent activity
is most correlated. This would account for the anatomical sharpening of
stripe borders (i.e., increased afferent segregation). Quantitative
autoradiographic analysis of 3H-glutamate binding to NMDA receptors
indicated that binding densities within the tectum did not differ between
control groups and NMDA chronically treated groups. We suggest that in the
experimental animals the response to NMDA may be decreased by a change in
the effectiveness of individual NMDA receptors rather than by decreases in
receptor number. This experimentally induced change may be analogous to
naturally occurring decreases in receptor function that correlate with the
end of some periods of visual plasticity in mammals.