2015 Theses Doctoral

Probing circuits for spinal motor control

Machado, Timothy Aloysius

Spinal circuits can generate locomotor output in the absence of sensory or descending input, but the principles of locomotor circuit organization remain unclear. We sought
insight into these principles by considering the elaboration of locomotor circuits across
evolution. The identity of limb-innervating motor neurons was reverted to a state resembling that of motor neurons that direct undulatory swimming in primitive aquatic vertebrates, permitting assessment of the role of motor neuron identity in determining locomotor pattern. Two-photon imaging was coupled with spike inference to measure locomotor firing in hundreds of motor neurons in isolated mouse spinal cords. In wild type preparations we observed sequential recruitment of motor neurons innervating flexor muscles controlling progressively more distal joints. Strikingly, after reversion of motor neuron identity virtually all firing patterns became distinctly flexor-like. Our interneuron imaging experiments demonstrate a new approach for functionally mapping the types of inputs that motor neurons might receive during locomotor firing. These data revealed that En1-derived inhibitory spinal interneuron activity appears to be dominated by a flexor-like pattern across the ventrolateral extent of the lumbar spinal cord–even in the regions surrounding flexor and extensor motor pools. Together, these findings show that motor neuron identity directs locomotor circuit
wiring, and indicate the evolutionary primacy of flexor pattern generation.