Spontaneous neuronal activity drives the establishment of normal structure and function in many regions of the developing nervous system. These inherent signals are shaped into the driving force behind massive, precise activity-dependent refinement of neuronal projections by the cellular and circuit properties of emerging networks. In the visual system of many mammals, retinal ganglion cells from each eye send projections into their principle target in the thalamus, the lateral geniculate (LGN). Spontaneous activity arising in the retina is necessary for refinement of the retinogeniculate projection into eye-specific layers. The proposed research uses an in vitro preparation of the neonatal mouse LGN that retains retinal inputs to ask if and how spontaneous synchronous activity arising in the retina might alter retinogeniculate synaptic efficacy, and whether such alterations drive the formation of eye-specific layers in the LGN. This work will test the hypothesis that developmental changes in retinogeniculate synaptic physiology, particularly in GABA (gamma-aminobutyric acid)-ergic synaptic transmission, are responsible for structural plasticity of the developing projection. These studies will further our understanding of the cellular basis for activity-dependent refinement of the visual system and provide insight into the organizing principles that govern normal and abnormal development in the human nervous system.
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