BRAIN EAGER: Novel Thermo-genetic Tools for Extrinsic Control of Neuronal Circuits

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

Brains can be thought of as networks of circuits. The neurons that make up these circuits interact to control behavior, but how the neurons do this is currently an open question. New tools are needed to learn how neuron networks produce behavior. One promising strategy would be to construct molecular switches that could flip neurons between active and inactive states. This project will investigate the potential to engineer a special group of proteins to make them serve as molecular switches that respond to changes in temperature. The proteins will be put into specific brain neurons of flies, and the fly's behaviors will be monitored in response to temperature changes that activate and deactivate the neurons. The fly is an accessible experimental model for these studies, and, additionally, what is learned in the fly brain will have broad relevance to other animal brains. The project will involve undergraduate and graduate students in the research and will provide them with interdisciplinary training in biophysics, neurophysiology, and behavior. Tools developed in the project have the potential to be used to understand other organ systems and will be shared with the wider scientific community. Individual Gustatory Receptor (GR) gene family members will be examined for temperature-dependent effects on nerve cell function. In one set of experiments, these GRs will be expressed in both sensory and non-sensory neurons in Drosophila melanogaster and tested for temperature responsiveness in heat-box behavioral assays. In a second set of experiments, natural- and chimeric-GRs will be expressed in Xenopus oocytes and COS cells and tested for temperature- and voltage-dependent kinetics of ionic current. Finally, natural- and chimeric-GRs will be expressed in sensory neurons in Drosophila and cultured cells and examined for physiological effects using live calcium imaging analysis.