UBC Theses and Dissertations
The role of adenylyl cyclase signaling pathways in developmental dendritogenesis in vivo Duncan, Blair
The period of early brain development involves an exceptional amount of neuronal morphological growth and refinement to form functional brain circuits. Although it is known that neural activity influences dendrite morphogenesis, the molecular pathways which convert a neural activity input to changes in morphology are not well understood. Here I show that activation of the adenylyl cyclase pathway promotes growth of developing brain neurons in vivo, in a neuron maturation-dependent manner. Rapid time-lapse two-photon imaging of single neuron growth within the developing vertebrate brain and pharmacological manipulations reveal a synergistic role for PKA and Epac in growth downstream of β-adrenergic receptors and adenylyl cyclase. Inhibition of the protease calpain increases axonal and dendritic filopodial density, but only in axons is this effect downstream of PKA. Furthermore, experiments indicate that PKA localization by AKAPs may be important in its regulation of dendritogenesis. Together, the results presented here outline multiple steps of a signaling pathway important in dynamic dendritogenesis and axogenesis in vivo.
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