Figure 1.

Strategies for targeting neurons in motor cortex based on their projection identity. (A) Injecting a retrograde tracer or viral vector into a region downstream of motor cortex (for example, the spinal cord) will label neurons in motor cortex that project to that area. (B) By expressing optogenetic activators such as Channelrhodopsin-2, neurons of the targeted projection class can be selectively activated while resulting movements are measured. Motor maps generated by stimulating specific projection classes can be tested for topographies of evoked movement direction and compared with maps from other projection classes. (C) Alternatively, the activity of labeled neurons can be measured while an experimental animal makes voluntary movements in different directions. This could be accomplished either with electrical recordings or by imaging genetically encoded calcium or voltage indicators. Again, preferred movement directions can be examined at different cortical locations for neurons in a given projection class, and different projection classes can be compared by performing retrograde injections in multiple structures targeted by cortical output neurons.