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Fine-structural alterations and clustering of developing synapses after chronic treatments with low levels of NMDA
L H Yen1, J T Sibley, M Constantine-Paton
1Department of Biology, Yale University, New Haven, Connecticut 06511.
Abstract:
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.
Insights
Chronic NMDA treatment in frogs alters synapse structure and arrangement in the visual pathway. This suggests NMDA raises the threshold for synapse stabilization, leading to selective loss and increased efficiency of remaining connections.
Area of Science:
- Neuroscience
- Synaptic plasticity
- Developmental neurobiology
Background:
- The visual pathway in frogs offers a model to study synapse stabilization in the central nervous system (CNS).
- Previous research indicated chronic NMDA treatment reduces branching in retinal ganglion cell (RGC) arbors in doubly innervated tecta.
Purpose of the Study:
- To investigate the fine-structural and synaptic rearrangement effects of chronic NMDA treatment on the retinotectal system.
- To understand the role of NMDA in synapse stabilization and its impact on synaptic morphology and organization.
Main Methods:
- Chronic low-level NMDA application to the optic tectum in frogs.
- Light and electron microscopy to analyze synaptic morphology and RGC arbor branching.
- Stereological analysis to quantify synaptic clustering and active zone characteristics.
Main Results:
- NMDA treatment caused thickening of pre- and postsynaptic densities in the superficial tectal neuropil.
- Synaptic changes were observed in doubly innervated tecta where RGC arbor pruning occurred, but not in singly innervated tecta.
- Increased incidence of multiple presynaptic profiles converging on a single postsynaptic process (synaptic clustering) was noted, without changes in active zone size or synapse density.
Conclusions:
- Chronic NMDA treatment appears to raise the threshold for synapse stabilization in tectal neurons.
- This leads to the selective elimination of less correlated synapses and enhances the efficiency and cooperativity of remaining synaptic contacts.