FINE-STRUCTURAL ALTERATIONS AND CLUSTERING OF DEVELOPING SYNAPSES AFTER CHRONIC TREATMENTS WITH LOW-LEVELS OF NMDA

In the visual pathway of frogs it is possible to apply low levels of N MDA chronically to the optic tectum and study the mechanisms underlyin g the stabilization of synapses developing within the CNS. Earlier stu dies (Cline and Constantine-Paton, 1990) found that chronic NMDA treat ment of tecta innervated by two retinas results in a reduction of bran ching within the terminal arbors of retinal ganglion cells (RGCs). We now report that this same chronic NMDA treatment produces fine-structu ral changes in synaptic morphology as well as local synaptic rearrange ments within the retinotectal neuropil. Chronic NMDA treatment of doub ly innervated tecta was associated with a thickening or darkening of b oth pre- and postsynaptic densities. These changes in synapse morpholo gy were restricted to the superficial neuropil of tecta in regions whe re reductions in branches of RGC axonal arbors were observed at the li ght microscopic level. The fine-structural effects were absent from si milarly treated tecta innervated by only one eye, where RGC axonal arb or 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 inc rease in the number of synapses per unit volume. These data are discus sed in the context of the hypothesis that chronic NMDA treatment raise s the threshold for synapse stabilization in tectal neurons, causing t he selective loss of poorly correlated synapses of both retinal and no n-retinal origin from tectal neuropil that is innervated by two retina s: increased pre- and postsynaptic thickening could reflect greater ef ficiency in the remaining synaptic contacts and their closer spatial p roximity on the same postsynaptic process is consistent with greater c ooperativity and less competition.