Sensory input is critical for object localization and recognition, and also to guide future movements of the whiskers. By collating our studies of long-range connections with previous data on thalamocortical (Bureau et al., 2006, Lu and Lin, 1993, Meyer et al., 2010b and Petreanu et al., 2009) and local cortical circuits (Hooks et al., 2011, Lefort et al., 2009 and Svoboda et al., 2010) it is possible to sketch out a circuit diagram for the cortical vibrissal sensorimotor loop in mice (Figure 8). Forces acting on whiskers excite sensory neurons in the trigeminal ganglion, triggering activity which ascends through the brainstem into VPM and L4 neurons in the barrel cortex (Petersen, 2007 and Svoboda

et al., 2010). L4 stellate selleck chemicals llc cells mainly excite L2/3 neurons, which in turn excite ABT-888 neurons in L5A and also in L5B (Armstrong-James and Fox, 1987, Brecht et al., 2003, Brecht and Sakmann, 2002, Hooks et al., 2011, Lefort et al., 2009 and Manns et al., 2004). A subset of L2/3 and L5A neurons project to vM1 (Figures S5A, S5B, and S9C), where they strongly target upper layer neurons in L2/3 and L5A, and only weakly deep layer neurons in L5B and L6 (Figures 4C–4F,

6, and S6). Upper layer neurons in vM1 receiving strong input from vS1 project back to vS1 (Figures 2B, 2C and 7B), where they synapse onto neurons in L2/3, L5A, and L5B (Petreanu et al., 2009). Cortico-cortical neurons in L2/3 and L5A in vM1 are thus the nexus of a powerful disynaptic feedback loop (vS1, L2/3/5A ←→ vM1, L2/3/5A), linking sensory and motor cortex (Figure 8). This until loop apparently violates the no-strong-loops principle which is thought to govern inter-areal connectivity in the visual system (Crick and Koch, 1998). Since AAV infected both L2/3 and L5A cells in vS1 (Figure S1A), additional experiments are required to determine the separate contributions of L2/3 and L5A neurons to activating targets in vM1 (Aronoff

et al., 2010). A small subset of deep L6 cells in vS1 also projected to vM1 (Figures S5A, S5B, and S9C). These neurons were only sparsely infected by the AAV virus, and their contribution to the vS1 → vM1 projection, although likely small in total, was underrepresented in our study. How does this superficial feedback loop communicate with the deep layer output neurons in vM1? The local circuit in somatic (Weiler et al., 2008) and vibrissal (Hooks et al., 2011) motor cortex shows a top-to-bottom organization. Interlaminar excitation is strongest from superficial layers downward, with a powerful descending projection from L2/3 to the border of L5A and L5B (Hooks et al., 2011). Weaker projections exist from L5A to L5B. Similarly, L2/3 and/or L5A neurons in vM1 excite L5B neurons in vS1 (Petreanu et al., 2009). L5B neurons in vM1 (Figures 2 and S5D) and vS1 (Matyas et al., 2010) are projecting to motor centers in the brainstem.