Max Planck Florida Corp

Sensory-motor Transformations in a Neural Circuit for Object-directed Walking - Walking Towards a Salient Object (prey, Mate, Etc.) Is a Basic and Conserved Behavioral Motif Shared Across Most Terrestrial Animals, Including Humans. Mobility Disorders Often Impact This Vital Function of Goal-directed Walking. Despite Varied Evolutionary Histories, Both Vertebrates and Invertebrates Have Converged on Similar Leg- Kinematics Strategies to Drive Changes in Walking Speed and Direction. Therefore, a Mechanistic Understanding of Goal-directed Walking, in Any Species, Is Critical and Will Have Broad Implications. Certain Descending Output Pathways of the Brain That Project to the Spinal-cord (vertebrates) or Ventral-nerve- Cord (invertebrates), Have Been Shown to Control Specific Aspects of Leg Movements Required for Directed Walking. However, How Sensory Inputs, Like Those Representing a Potential Mate, Engage Appropriate Combinations of Descending Pathways to Move the Animal as Intended, Remains an Open Question. This Gap Is Due to Two Major Challenges: 1) Defining a Clearly Resolved Sensory-motor Neural Circuit Underlying Object-directed Walking, and 2) Measuring and Perturbing Combinations of Descending Pathways That Govern the Leg Movements Required for Object-directed Walking. We Propose to Overcome These Challenges by Using the Well-established Drosophila Model System. in the Proposed Work, We Will Evaluate How Physiology and Connectivity Within a Defined and Genetically Accessible, Multi-layered Neural Circuit (the DNP09 Input-output Circuit) Transform Object-tracking Sensory Input Into Directed-walking Output. to Enable This, We Developed New Experimental and Modeling Approaches, That Provide High-fidelity Access to This Neural Circuit at Cellular and Synaptic Resolution. We Will First Use Whole-cell Electrophysiological Recordings and Biophysically Detailed Full Morphology Models to Examine How Synaptic Layout of Specific Visual Pathways Recruit the DNP09 Network During Object-directed Turning Events. We Will Then Use Novel Calibrated Stimulation Techniques and Connectome-constrained Network Models to Characterize How DNP09 Recruits a Population of Interconnected Descending Neurons That Are Poised to Control Directed Walking. Through a Combination of Modeling and Experiments Leveraging Two-photon Holography and High-resolution Kinematics Analysis, We Will Then Extract How Descending Neuron Population Activity States Encode Directed Walking Maneuvers. the Proposed Efforts Will Determine How Sensory-evoked Naturalistic Activity Propagates Across a Network of Interconnected Neurons to Drive the Distributed Control of Motor Outputs Required for Generating Object-directed Walking. the Long-term Objective of This Work Is to Provide Cross-species Transferable Models of How Combinations of Brain Output Pathways Orchestrate the Downstream Motor Circuits for Executing Appropriate Locomotor Outputs, a Fundamental Problem in Understanding How Brains Control Behaviors.