25% F&A Subproject for In Vivo analysis of Motor Cortext Projection Neurons

Volitional movements and motivated behaviors rely fundamentally on the motor areas of the cerebral cortex. The behavioral functions of the motor cortex are mediated by its projection neurons – excitatory pyramidal neurons that deliver signals from motor cortex directly to downstream areas in the motor system, such as the spinal cord and basal ganglia. Recently, using primarily brain slice methods including photostimulation and retrograde labeling, we have elucidated important cellular/synaptic principles governing the local-circuit organization of corticospinal and corticostriatal neurons, the two major classes of layer 5 pyramidal neurons in motor cortex. Our findings have led to testable hypotheses about the in vivo functions of these neurons during motor behavior. We therefore now propose an experimental program aimed at translating our ex vivo approaches to in vivo paradigms, in an effort to understand the in vivo activities of key cell classes in motor cortex involved in motor control. These studies are designed to provide foundational new knowledge about how cortical projection neurons generate signals to different subcortical areas involved in the control of movement in mammals.