CNI Seminar: Tim Machado

Tim Machado
Department of Neuroscience
University of Pennsylvania

Brainwide circuits for descending command and control

Even seemingly simple movements require complex, context-dependent processing of sensory signals and motor commands. How does the joint activity of neural circuitry distributed across the brain subserve motor behavior? To address this question, we first studied context-dependent motor behaviors in head-restrained mice using a widefield optical imaging method, Cortical Observation by Synchronous Multifocal Optical Sampling (COSMOS), to record with true simultaneity from over a thousand neuronal sources spread across the entire curved surface of mouse dorsal neocortex. Using a memory-guided lick-to-target task, we found that targeted licking actions are encoded by distributed neural activity throughout the cortex, with no apparent spatial structure. We also found that across cortex, unaveraged (but not trial-averaged) activity correlations showed local structure. Finally, analysis of population dynamics revealed similar encodings of history-guided motor plans in even sensory areas of cortex.

But how are these widespread representations transformed into motor output? To address this question, we measured neural activity in medullary circuits while kinematically similar licks were made towards three spouts in different behavioral contexts. During this behavior, we optogenetically inhibited cortex (using VGAT-ChR2 mice), and using 3D kinematic tracking, we revealed that cortical silencing influenced licking movements in a context-specific manner (i.e. it selectively affected long-distance licks to the middle spout, but not closer licks to the side spouts). We subsequently obtained simultaneous recordings from the cortex and the medulla to analyze the effects of this perturbation along the output pathway between cortex and the medulla. We found units modulated by cortical inhibition in both cortex and the medulla. Together, these results advance our understanding of how distributed representations and descending commands drive specific movements.


A pizza lunch willl be served.