Presynaptic Regulation of Dendritic Structural Dynamics

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DESCRIPTION (provided by applicant): A central goal in developmental neuroscience is to elucidate the cellular mechanisms behind the formation, refinement, and maintenance of neural circuits, An experimental strategy for studying these mechanisms is time lapse imaging of morphological changes in dendritic arbors; while imaging studies have shown that presynaptic neural activity influences dendritic structure, the parameters of presynaptic activity that influence postsynaptic morphology remain unclear. For example, in the optic tectum of Xenopus tadpoles, visual stimulation enhances tectal cell dendritic growth; however, it is unknown whether elevated retinal ganglion cell activity or stimulus induced correlations amongst retinal ganglion cells are responsible for the additional growth. By characterizing ganglion cells' spontaneous activity and their responses to a variety of visual stimuli, it will be possible to develop visual stimuli that systematically manipulate their firing rates and correlations. Playing these stimuli to tadpoles while monitoring the structural dynamics of individual tectal cell dendritic arbors, will directly test the importance of presynaptic activity levels and correlations for regulating postsynaptic morphology. In addition, by correlating the activity of some retinal ganglion cells, but not others with comparable activity levels, it is possible to determine whether or not tectal cells prefer initiating and/or stabilizing contacts with correlated inputs. Finally, imaging the dendritic arbors of tectal cells whose ability to spike has been genetically reduced, will distinguish whether or not tectal cell action potentials are required for presynaptic regulation of tectal dendrites. Greater understanding of the features of presynaptic activity relevant to dendritic structural plasticity, and therefore neural circuit formation, will reveal much about the underlying cellular mechanisms. In particular, the compatibility of spike timing dependent synaptic plasticity and dendritic structural plasticity will be tested. These studies will help us understand how retinal activity impacts wiring in visual circuits deeper in the brain. This knowledge will allow us to better predict whether some eye diseases that impact retinal activity might also cause previously undetected wiring defects in these circuits and design strategies to prevent, ameliorate, or compensate for these defects.