Motor cortex (M1) plays a crucial role in the control of voluntary movement but the neuronal mechanisms by which this region converges on downstream circuits remain obscure. To better understand how activity in M1 is translated into context-appropriate behaviors, we propose to characterize the role of specific cortical projection subtypes as defined by their spinal interneuron targets. A growing body of electrophysiological and behavioral evidence suggests that interneuron subsets in the spinal cord represent functional units that, when recruited, play a role in imposing a task-appropriate pattern of muscle activation. An example of this is seen in the alternating activity of opposing flexor and extensor muscles, which is in part regulated by defined spinal circuits. These circuits can be over-ridden to achieve simultaneous antagonist muscle coactivation. Two inhibitory spinal interneuron (IN) populations, presynaptic GABAergic (GABApre) and reciprocal inhibitory GABA/glycineric (Ia) neurons, play a role in this transition, undergoing activation or suppression of their activity, respectively. Using a recently developed CVS-N2C based rabies tracing strategy combined with genetic access to specific cardinal interneuron populations, we have identified that both classes receive direct corticospinal neuron (CSN) inputs. Moreover, this input has been suggested to play a role in the task-appropriate switching from alternating activation to co-activation of flexor-extensor muscle pairs. In order to investigate the nature of this role, we have developed a motor behavioral task in, which mice are trained to either alternate or co-contract opposing forelimb muscles in response to a visual cue. For the first time, we can now simultaneously monitor and manipulate the activity of defined subsets of CSNs during a motor-cortically dependent behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19NS104649-03
Application #
9775475
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Russo, Abigail A; Bittner, Sean R; Perkins, Sean M et al. (2018) Motor Cortex Embeds Muscle-like Commands in an Untangled Population Response. Neuron 97:953-966.e8
Lara, A H; Cunningham, J P; Churchland, M M (2018) Different population dynamics in the supplementary motor area and motor cortex during reaching. Nat Commun 9:2754
Lara, Antonio H; Elsayed, Gamaleldin F; Zimnik, Andrew J et al. (2018) Conservation of preparatory neural events in monkey motor cortex regardless of how movement is initiated. Elife 7:
Hillman, Elizabeth Mc; Voleti, Venkatakaushik; Patel, Kripa et al. (2018) High-speed 3D imaging of cellular activity in the brain using axially-extended beams and light sheets. Curr Opin Neurobiol 50:190-200