Mobility is a fundamental aspect of human quality of life. As the longevity of the planet's population grows, there is great concern that age-related locomotor disability will become an increasingly heavy burden to individuals, families, and governments alike. Accommodating such a massive demographic shift demands not only a widespread public health response, but the pursuit of ever-improving models of neurodegenerative locomotor decline as the basis for novel preventative measures and therapies. In this proposal I describe a systematic approach to determining the extent and character of neural connectivity within circuits that mediate many aspects of coordinated walking in adult Drosophila melanogaster. This approach takes advantage of the unprecedented functional resolution of an optics-based locomotor assay to isolate cellular components of adult Drosophila neural circuits that mediate specific aspects of coordinated walking. I describe a multi-step thermogenetic screening scheme that, in combination with intersectional binary expression systems and a recently optimized technique to visualize synaptic connectivity, will allow me to probe the functional output and connectivity of locomotor circuits at the level of the single cell.
The nervous system is defined by its immense connectivity;to assume that it develops and ages simply as a cluster individual cells rather than a complex and dynamic network of modular units severely limits our ability to address the growing burden of neurodegenerative disease in an aging population. Identifying and characterizing locomotor circuits in the genetically tractable and physiologically accessible Drosophila model will lay the groundwork for studying neural development and neurodegeneration as phenomena that take place in the context of a highly integrated neural network.
|Enriquez, Jonathan; Venkatasubramanian, Lalanti; Baek, Myungin et al. (2015) Specification of individual adult motor neuron morphologies by combinatorial transcription factor codes. Neuron 86:955-970|