And in the likelihood that there are dozens of motor-relevant interneuron classes, the task of delineating their connections, while daunting, cannot be ignored. The perturbation of molecularly defined interneuron classes has revealed disruption of elements of locomotor output (Goulding, 2009). The encoding of left-right alternation seems particularly fragile, implying that the circuits that enable the opposition of contralateral limb movement are more susceptible to the loss of individual interneuron types. In contrast, BI6727 the neurons that control flexor-extensor alternation and rhythm generation

have been harder to pinpoint or disrupt, suggesting that emergent circuit functionality might be robust enough that no single subtype is indispensable for these tasks. Thus, while some features of motor systems appear assigned to individual interneuron types, many functions are likely to be more widely distributed among populations GSK1349572 manufacturer (Briggman and Kristan, 2008). Thus, interneuronal diversity likely contributes

to functional flexibility in spinal circuits both by enabling discrete subtypes to play distinct roles and by enabling diverse interactions among interneurons that support a broader array of emergent behaviors. How do descending systems exploit the anatomical and functional features of spinal circuit organization in the selection of task-specific motor output? As emphasized, the ambiguities of spinal circuit architecture limit any understanding of the way in which CSMN inputs engage spinal circuits. Nevertheless, questions about descending cortical organization and its translation can be posed in the dialect of spinal interneuronal networks. Do some CSMNs serve as specifists and target particular interneuron subtypes, while others serve as generalists and engage a range of subtypes (Figure 1C)? Do some interneuron subtypes simply evade CSMN input?

Do CSMNs target spinal interneurons selectively, on the basis of their “degree of separation” status, or their role in pattern generation? Do distinct CSMNs target zero-, first-, Calpain and even second-order interneurons? And just how many different subtypes of CSMNs are there? The more complete the molecular definition of spinal interneuron subtype, the easier it will be to resolve these questions. Practically, methods for retrograde transsynaptic tracing from, and anterograde synaptic mapping onto, defined interneuron subtypes are now working (Arber, 2012), and the major limitation may simply be to define better the molecular grain of interneuron diversity. At a functional level, the engagement of spinal interneurons by CSMNs could provide insight into the mechanisms of motor state switching. The coordination of muscle contraction with reduced activation of antagonist muscles via reciprocal inhibitory pathways has long been established (Sherrington, 1897).