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Molecular mechanisms integrating genetic and calcium activity-dependent neurotransmitter specification
Abstract
Excitability regulates many aspects of neuronal differentiation in addition to forming the basis for rapid signaling in the mature nervous system. Several key features that determine the functional activity of neurons are modulated by calcium signaling during development, including neurotransmitter specification. The focus of the dissertation is on understanding the signaling cascades that mediate calcium spike-dependent specification of neurotransmitter phenotype in embryonic spinal neurons. I describe the identification and characterization of novel pathways that act in the specification of activity- dependent neurotransmitter phenotype by targeted screening of molecules known to regulate the expression of excitatory and inhibitory neurotransmitters. In addition, I describe a gain-of-function screen to identify novel molecules that were previously unknown to play a role in the activity-dependent specification of neurotransmitter phenotype. Finally, I describe the generation and development of novel transgenic Xenopus lines in which specific subsets of neurons are fluorescently labeled. These lines serve as the basis for further genetic screening and can be used to characterize the activity- dependent specification of neurotransmitters as well as numerous other processes in neuronal development
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