How do genetic and neural networks shape social behavior?
Aggression is an innate behavior that evolved in the framework of defending or obtaining resources. However when expressed out of context, unchecked aggression and violence have destructive consequences. In addition to the significant toll on society in terms of direct violent acts, the symptoms of aggression are often present in neurological disorders such as Alzheimer’s disease, bipolar disorder, and other mood disorders. Model systems that allow examination of distinct neuronal networks at the molecular, cellular and circuit level can aid immensely in our understanding of the biological basis of behavior and should be relatable to other species up to and including man. The overall research goal is to understand how neuronal networks are assembled to mediate aggressive behavior. Currently, we are studying the octopamine (OA) neuronal system as a key component in the male behavioral choice response.
Drosophila as a model for MeCP2 Duplication Syndrome:
A second project in the lab is addressing fundamental mechanisms of MeCP2 function in microcircuit function and regulation of MeCP2 expression in glial cells. Methyl-CpG-binding protein 2 (MeCP2) is one of the most dosage-sensitive genes involved in neuronal functional integrity. Altered levels of MeCP2 either through loss-of-function mutations (Rett Syndrome (RTT)) or increased protein levels due to gene duplication (MeCP2 Duplication Syndrome), result in dramatic phenotypes including mental retardation, motor dysfunction, features of autism, stereotyped hand movements, and sleep disturbances, and are known collectively as MeCP2 spectrum disorders (MSD). Using Drosophila as a model organism, we are examining the cell-type specific effects of MeCP2 function on microcircuits controlling sleep behavior, utilizing high-resolution 3D imaging to examine microcircuit synaptic connections, and undertaking genomic approaches to identify gene products which down-regulate astrocytic MeCP2 expression. Understanding how mutations in MeCP2 or altered MeCP2 protein levels affects neuron, microcircuits, and target gene expression will provide insight into a large group of MeCP2-associated disorders.