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Mechanism for Spontaneous Calcium Activity and Spinal Cord Neurotransmitter Specification, and the Role of Calcium Activity in Dopamine Specification in the Brain and Spinal Cord

Abstract

Spontaneous electrical activity is a feature of the nervous system from early stages of development preceding synapse formation. An example of this is calcium-spike activity, which is displayed by embryonic Xenopus laevis spinal cord neurons, and has a role in neurotransmitter specification. Here I present data identifying a mechanism for calcium-spike activity that depends on GABA or glutamate activation of metabotropic receptors, and their recruitment of PKA or PKC. This work attributes a role to neurotransmitters and metabotropic receptors prior to synapse formation in modulating electrical activity that in turn modulates neurotransmitter specification. These results contribute to our knowledge of the molecular mechanisms recruited during development. In addition to electrical activity, transcription factors play a role in neurotransmitter specification. Here I present a study of the development of the dopaminergic system in Xenopus laevis to characterize the co-expression of dopamine with additional neurotransmitters, and with transcription factors. This led to identification of subclasses of dopaminergic neurons based on these markers. Calcium-spike activity plays a role in dopamine specification, but different dopaminergic nuclei respond to activity manipulations in a different way. Examination of the in situ calcium spike activity of spinal cord neurons showed that neurons with different molecular markers have distinct pattern of calcium-spike activity. These results provide the basis for further studies to establish the interplay between calcium-spike activity and transcription factors in the dopaminergic system

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