Journal of Neuroscience, Vol 13, 4949-4960, Copyright © 1993 by Society for Neuroscience
Fine-structural alterations and clustering of developing synapses after chronic treatments with low levels of NMDA
LH Yen, JT Sibley and M Constantine-Paton
Department of Biology, Yale University, New Haven, Connecticut 06511.
In the visual pathway of frogs it is possible to apply low levels of NMDA
chronically to the optic tectum and study the mechanisms underlying the
stabilization of synapses developing within the CNS. Earlier studies (Cline
and Constantine-Paton, 1990) found that chronic NMDA treatment of tecta
innervated by two retinas results in a reduction of branching within the
terminal arbors of retinal ganglion cells (RGCs). We now report that this
same chronic NMDA treatment produces fine-structural changes in synaptic
morphology as well as local synaptic rearrangements within the retinotectal
neuropil. Chronic NMDA treatment of doubly innervated tecta was associated
with a thickening or darkening of both pre- and postsynaptic densities.
These changes in synapse morphology were restricted to the superficial
neuropil of tecta in regions where reductions in branches of RGC axonal
arbors were observed at the light microscopic level. The fine- structural
effects were absent from similarly treated tecta innervated by only one
eye, where RGC axonal arbor pruning was not observed. Stereological
analyses indicated that the incidence of two or more presynaptic profiles
converging on the same postsynaptic process was significantly increased in
the NMDA-treated, doubly innervated tecta. This observed increase in
synaptic clustering was not associated with a larger synaptic active zone,
or with an increase in the number of synapses per unit volume. These data
are discussed in the context of the hypothesis that chronic NMDA treatment
raises the threshold for synapse stabilization in tectal neurons, causing
the selective loss of poorly correlated synapses of both retinal and
non-retinal origin from tectal neuropil that is innervated by two retinas:
increased pre- and postsynaptic thickening could reflect greater efficiency
in the remaining synaptic contacts and their closer spatial proximity on
the same postsynaptic process is consistent with greater cooperativity and
less competition.
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