Periodic Reporting for period 1 - HEALTHYSYNAPSES (Molecular mechanisms underlying synaptic maintenance and rejuvenation)
Reporting period: 2016-03-01 to 2018-02-28
Under certain conditions, autophagy is reduced and this can be linked to neurodegeneration while in other conditions, specific types of autophagy are upregulated. These data suggest that both an up regulation and down regulation of autophagic mechanisms can have deleterious effects on synapses and neurons. My optogenetic tools also show that increasing autophagy specifically at the synapse can have effects on synapse function and growth. Given that both increased and decrease synaptic autophagy seems to be disadvantageous, it seem synaptic autophagy is a very tightly regulated process. The age and disease condition dependent change in synaptic function is also correlated with changes in synaptic electrophysiology and behavioural alterations (for e.g. decreased motor function) that suggest nervous system dysfunction. In order to deepen our understanding of synaptic autophagy, a genetic screen of nearly 5000 Drosophila mutants was conducted and several genes have been isolated that specifically rescue dysfunctional synaptic autophagy. In my future studies, I will use these candidate genes to gain an even deeper understanding of the network of synaptic autophagy present in the nervous system.
These results have been presented in oral and poster format at several national and international conferences. Furthermore, we have several manuscripts in preparation describing these findings that will be published soon.