Determining how neuronal connections become highly organized early in life is fundamental to understanding of how the nervous system develops. Precise patterns of neural connections emerge during development as inappropriate connections are eliminated, and appropriate ones are maintained. This competitive process is driven by neuronal activity such that cells that """"""""fire together, wire together."""""""" Connectivity in many parts of the developing visual system undergo restructuring through processes driven by action potential activity from the retina, even before the onset of vision. This proposal addresses the role of spontaneous periodic bursting activity in establishing functionally discrete projections from the retina to its central targets in the ferret. Specifically it focuses on how the innervation patterns of ON and OFF retinal ganglion cells are refined during development by mechanisms based on temporal differences in their spontaneous bursting patterns.
Specific aim 1 addresses what cellular interactions occur in the inner retina to create distinct spontaneous activity patterns of ON and OFF ganglion cells at appropriate periods in development. Interactions mediated by GABA and glutamate will be investigated using electrophysiological and calcium imaging techniques.
Specific aim 2 is to determine the temporal relationship between the bursting rhythms of ON and OFF cells, and investigate what information in their activity pattern could to segregation of their connectivity. Correlated activity between ON and OFF ganglion cells will be examined by recording extracellularly from pairs of cells. Modeling techniques will be used to test and predict how spontaneous patterns in ON and OFF ganglion cells can specify ON and OFF retinogeniculate connectivity.
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