University of New Hampshire
Neuroscience and Behavior
Mentor: Dr. Arturor Andrade, Department of Biological Sciences
Dissecting Cell-Specific Roles Of α2δ-Proteins In Seizure-Like Activity Of Drosophilia Melanogaster (fruit fly)
Lyrica and Gabapentin are anticonvulsant medications that interact with α2δ-proteins to treat seizure-like activity. The α2δ-protein subunits of voltage gated calcium channels are extracellular and dynamically aid in synaptic transmission. The need to understand the cell specific expression patterns of α2δ-proteins may indicate a mechanistic function that links α2δ- protein dysfunction to seizure-like behavior. The two conserved α2δ-proteins of D. melanogaster (fruit fly), CG42817 and CG4587, will be used to investigate whether a2d protein disruption induces seizure-like behavior. Understanding the cell-specific role of α2δ-proteins can provide insights on increasing the specificity of anticonvulsant drugs used to treat epilepsy. A bioinformatic analysis quantifying gene expression done by the Allen Institute for Brain Science© (2004) indicated a cell-specific expression of α2δ genes within inhibitory and excitatory cell populations. The relevance of this cell-specific expression is currently unknown but understanding the cell-specific role of α2δ-proteins can provide insights for the creation of drugs that better target seizure-like symptoms. To assess the function of α2δ-proteins in the fruit fly, we will knock down expression of the CG42817 and CG4587 α2δ proteins within excitatory and inhibitory cell-specific populations. Transgenic fly lines expressing knocked down α2δ-gene expression will be used to evaluate seizure-like behavior. Using the behavior elicited from flies with knocked down α2δ expression, we hope to answer whether either CG gene is sufficient to impair seizure-like activity in the fruit fly. If either CG gene is associated with seizure like behavior, this will reveal a2d proteins as effective targets for medications used to treat epilepsies.