Visualizing Remodeling at the Retinogeniculate Synapse

摘要

ABSTRACT The formation of precise synaptic connections in the developing central nervous system (CNS) is critical for neurological function. At the retinogeniculate synapse, the connection between the retina and the lateral geniculate nucleus (LGN) of the thalamus, several developmental phases contribute to the formation, refinement and maturation of synatic circuits. After the initial mapping of a neuron to its target, there is gross morphological rearrangement of the axon arbors, as retinal ganglion cell (RGC) axons segregate into eye-specific layers. In the mouse, we have found that long after RGC axons segregate into the proper region of the LGN (postnatal day 8, p8), there are two periods of robust synaptic plasticity and remodeling. The first phase of synaptic plasticity occurs around the time of eye opening (p12-14) when some of the retinal inputs to a given LGN relay neuron strengthened while other inputs are pruned. A second, previously undetected, phase of plasticity occurs after p20, when the strength and connectivity of the retinogeniculate synapse becomes sensitive to sensory experience. Here we propose to study the morphological changes of retinal axon arbors that correspond to the two periods of synaptic plasticity. To do this, we will take advantage of available transgenic mice, and also generate new mouse lines in which a sparse subset of their RGCs co-express labels that tag axon arbors and the presynaptic marker, synaptophysin, using different fluorescent colors. Using these mice, we will examine changes in the morphology of select retinal ganglion cell axons and the relative distribution of the synaptic contacts within an axon arbor territory. These changes will be quantified as the connection remodels during normal development, and in response to visual deprivation during the second phase of plasticity. We will test the hypothesis that the RGC axon arbor structure is broader that functionally necessary and becomes stable around the time of eye opening. We will also examine whether the periods of robust synaptic plasticity represent rearrangements of synaptic release sites within a fixed axon arbor scaffold. A finding of a broad structural scaffold in which synaptic contacts can form, break and rearrange may represent a relatively novel type of neural plasticity. By relating structure to function, we hope to gain clearer understanding of the structural mechanisms that underlie synaptic development.