Behavioral consequences of electrical versus chemical synapse restoration in a drosophila model of neurodegeneration

Résumé

In this thesis we have documented the behavioral consequences of synapse restoration employing Drosophila melanogaster as a genetic model. Here, we have characterized the role of electrical synapses in olfactory perception after eliminating the electrical connections in fly brain or by attenuating them in the whole brain and in selected neuronal populations of the olfactory pathway. Besides, we have also analyzed fly olfactory responses after their restoration. Our findings revealed that alterations in electrical connections yield to behavioral changes in an odorant- and concentration- manner and how their selective restoration allows the rescue of normal olfactory responses. In addition to their role in olfaction, this thesis also highlights the relevance of electrical synapses in life expectancy and locomotion. Again, the selective restoration of electrical synapses in whole fly brain and in selected neuronal populations improves fly viability and locomotor activity. Furthermore, this thesis also describes the beneficial synaptogenic and neuroprotective effects triggered by phosphoinositide 3 Kinase (PI3K) activation in a Drosophila model of neurodegeneration, based on the expression of a human variant of Aβ42 peptide. Our findings reveal that negative effects on olfaction, locomotion and life expectancy elicited by Aβ42 peptide are ameliorated by PI3K expression in Drosophila neurons.