Grant: Discovery Grants Program - Individual

Complexins constitute a family of cytosolic proteins that are involved in the regulation of neurotransmitter release. Complexin I is considered a marker of inhibitory synapses, while complexin II (Cpx II) labels predominantly excitatory nerve terminals. Although it is clear that neurotransmitter release occurs at the presynaptic terminal, recent evidence suggest that astrocytes possess the same neuronal machinery used for synaptic vesiclar release. Since Cpx II is an integral part of this neuronal machinery, we plan to study its role in the release of glutamate from these glial cells. The research project will address hypotheses that consider 1) Cpx II is present in astrocytes and regulates the release of glutamate from these cells, 2) Cpx II II modulates synaptic neurotransmission, 3) Oxidative stress influences Cpx II-mediated glutamate release, and 4) Cpx II regulates a novel and distinct form of astrocytic glutamate release that is different to other types of glutamate release operating under conditions of pathology. These issues will be addressed using primary cultures of astrocytes and neurons, in which knockdown of Cpx II gene expression will be produced and consequential genomic effects of altered Cpx II function will be identified in astrocytes and neurons along with energy metabolism changes. We are confident this research project will not only increase our understanding of the role of complexins in astrocyte function, but will also provide new insight into the significance of glutamate release from these cells, the influence of this process on excitatory neurotransmission, and its vulnerability under pathological conditions.