These recordings confirmed that glutamate receptor antagonists blocked synaptic input to the cortex driven by electrical stimulation of the contralateral forelimb. Glutamate receptor antagonists did not block direct activation of ChR2, but they did cause a decrease in

delayed, presumably synaptic, components (Figure 7A). ABT-199 This effect was evident at all depths recorded (Figure 7B), but may have been primarily due to inactivation of the upper cortical layers, where drug concentrations are expected to be highest after topical application. Because optogenetic stimulation of ChR2-expressing neurons does not require synaptic activation, corticofugal neurons could still propagate their action potentials beyond the influence of the cortically applied glutamate receptor antagonists to evoke movements. The fact that cortical application of glutamate receptor antagonists does not abolish movement topography (Figure 6) or prevent direct activation of corticofugal ChR2-expressing neurons (Figure 7) suggests that cortical output circuits may differentiate the Mab and Mad subregions. To test this hypothesis, we injected the deep cortical layers of Mab and Mad with adeno-associated virus containing fluorescent marker constructs to label axonal projections throughout the brain (Figure 8A). In addition to reciprocal intracortical projections

between find more these regions and trans-callosal projections to homotopic sensorimotor cortex, we observed adjacent, nonoverlapping projections in the striatum and internal capsule Astemizole (Figures 8B and 8C), with fibers originating in Mab occupying positions medial to those from Mad (2.0 ± 0.1 versus 2.5 ± 0.07 mm from midline in the dorsolateral striatum, p = 0.03, n = 7, paired t test; Figure 8D). This observation further supports the hypothesis that movement map topography is a product of the pattern of corticofugal projections, whereas the generation of complex movements by prolonged stimulation requires input from recurrent intracortical circuits and/or loops with subcortical structures. We have applied

light-based motor mapping to reveal that the mouse forelimb motor cortex is subdivided into distinct movement representations. Prolonged stimulation of these regions drives movements with similar speed profiles, but which terminate at different positions in space. Although complex movements evoked by prolonged stimulation were sensitive to perturbations of intracortical synaptic transmission, the topography of movement direction was not abolished by blockade of either excitatory or inhibitory synaptic transmission. The persistence of movement topography in spite of disrupted intracortical synaptic transmission may be due to the presence of segregated corticofugal pathways from the two movement representations. Functional differences between movement representations are likely the product of both their intracortical circuits (Jacobs and Donoghue, 1991 and Rouiller et al.