Roles of mitochondria and inhibitor of apoptosis proteins in the spatial and temporal regulation of caspase activation during axonal arborisation and degeneration

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The overall aim of our research is to understand the cellular and molecular mechanisms of axonal branching and synapse formation, key steps in the establishment of neuronal connectivity. We use the zebrafish visual system as a model for studying the cellular and molecular mechanisms of arborisation and synapse formation using the retinal ganglion cell axon arbors. We can perform in vivo imaging to follow their dynamics and manipulated the the function of potential genes playing roles. We have found that mitochondria are preferentially localised to stable presynaptic sites and branches rather than in the new / young highly dynamic branch tips and presynaptic sites. These data suggest that mitochondria may play roles at stable synapses that are more likely to be electrically active in neuronal circuits where higher amounts of ATP are necessary to maintain neural activity. We have also monitored a rapid switch in caspase activity in retinal axon arbors at the onset of neurodegeneration. There is a loss of spatially restricted caspase activation to a more widespread which may contribute to the neural degeneration observed. The mechanisms of which are currently unknown - to allow rapid and more spatially restricted caspase activation.