Context-dependent neural processing of leg proprioception in Drosophila

本体感觉对有效的运动控制至关重要：本体感觉系统的功能障碍会损害

Proprioception is critical for effective motor control: dysfunctions of the proprioceptive system can impair balance, motor coordination, and motor learning. However, despite its importance, little is known about the initial stages of proprioceptive processing in any animal, nor how this information is modulated by behavioral state. I propose studying proprioception in the fly, D. melanogaster, whose proprioceptive system is more experimentally accessible than that of vertebrates, but still analogous in its organization and function. I will combine experimental and computational methods to study the flow of information from the proprioceptive sensory structure, the femoral chordotonal organ, into genetically identifiable downstream circuits. In particular, I will characterize how neural encoding changes during self vs. externally-generated movements, and how proprioceptive information enters the brain to inform motor planning. Test how perturbing specific inputs changes central encoding of imposed tibia movements. I will use patch- clamp electrophysiology to record the activity of second-order proprioceptive neurons while moving the leg along naturalistic and broadband, pseudo-random trajectories. I will then build a linear/nonlinear model to determine the computations performed by each cell type. I will perturb inputs to central neurons and determine how these perturbations alter neural encoding of leg movements. Test the hypothesis that self- vs. externally-generated motions are differently encoded by some neurons. I will record the activity of second-order neurons while the fly moves its leg. I will then replay those movements and determine which neurons differently encode self- vs. externally-generated movements. I will characterize how a neuron’s encoding changes and determine if there is an internal estimate of state expectations. Determine how proprioceptive information entering the brain integrates with behavioral state and information from other mechanoreceptors. Preliminary anatomical data suggests that a region of the brain, the wedge, integrates multimodal mechanosensory cues from the legs and antennae. I will use 2-photon calcium imaging to determine what proprioceptive information is relayed to this area and whether leg movement attenuates antennal signals. I will then focus on how the central complex, a brain region important in motor planning, receives proprioceptive input. I will use intracellular recordings and calcium imaging to ask which central complex neurons encode proprioceptive information. My long-term goal is to run my own research group focused on the function and evolution of the fly proprioceptive system. Toward this end, my postdoctoral training is focused on the following goals: honing my computational skills, developing management and mentoring skills, publishing and presenting my research, and securing an independent, tenure-track position. I will be co-mentored by Drs. John Tuthill and Adrienne Fairhall in the Physiology and Biophysics department at the University of Washington.