Longitudinal structure of spinal premotor circuits

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Project Summary As animals locomote, they constantly coordinate activity between the rostral and caudal ends of the body. This coordination relies on neurons in the spinal cord that send long ascending or descending axonal projections. Although several studies have shown that ablation of these neurons leads to deficits in coordination, it is largely unknown whether these long-range circuits are similar or different from local circuits. In recently published data in larval zebrafish, we demonstrated that at least one genetically defined class of spinal neurons, the V1 (En1+) population, changes its synaptic targets as its axon ascends in the spinal cord. Specifically, V1 neurons form synaptic connections with motor neurons and other ventral horn neurons nearby, but switch to inhibiting a dorsal horn sensory population at longer range. Here we propose to extend this analysis to five additional sets of ventral horn neurons, the dI6, V0 excitatory and inhibitory, V2a, and V2b populations. To create this large-scale circuit map, we use localized optogenetic activation of identified spinal populations while carrying out whole-cell recording of identified potential postsynaptic partners. By translating the optogenetic stimuli up and down the spinal cord, we can build a physiological map of the strength of the synaptic connection at various rostrocaudal positions. Normalization of the synaptic charge transfer allows comparisons across target populations, providing a comprehensive grid of connectivity among spinal neuron classes at various rostrocaudal distances. We will then build a computational model of spinal cord connectivity that reflects biological reality, as measured in these experiments. Using this model, we will test the consequences of shifting synaptic connections in the rostrocaudal axis, in order to understand the logic of spinal circuit organization. Finally, we will selectively ablate long-range or local V2a neurons to determine the behavioral effects of long-range vs local projections. Together, these experiments will provide a circuit map of genetically identified spinal neurons.