Optogenetic dissection of a behavioural module in the vertebrate spinal cord

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Abstract
In the brief period during which we have known of their existence, light-gated ion channels have been used to assess the function of known cell types to which they are genetically targeted. Here Wyart et al. search for unknown cell types that drive the central pattern generator of locomotion. GAL4 lines of zebrafish in which light-gated glutamate receptors were sparsely expressed in diverse, partially overlapping sets of neurons were screened. Common behavioural effects of light could thus be attributed to activity in a specific cell type when it is the only cell shared between the different lines. The photo-stimulation of one specific cell type, the Kolmer–Agduhr cell, was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. Genetically silencing Kolmer–Agduhr cells reduced the frequency of spontaneous free swimming, indicating that Kolmer–Agduhr cell activity provides necessary tone for spontaneous forward swimming. Kolmer–Agduhr cells have been known for over 75 years, but their function has been mysterious. This work shows that during early development in low vertebrates these cells provide a positive drive to the spinal central pattern generator for spontaneous locomotion. In vertebrates, the excitatory synaptic drive for inducing spinal central pattern generators (CPGs) — which are responsible for generating rhythmic movements — can originate from either supraspinal glutamatergic inputs or from within the spinal cord. A spinal input to the CPG is now identified using a combination of intersectional gene expression and optogenetics in zebrafish larvae; the results reveal that during early development Kolmer–Agduhr cells provide a positive drive to the spinal CPG for spontaneous locomotion. Locomotion relies on neural networks called central pattern generators (CPGs) that generate periodic motor commands for rhythmic movements1. In vertebrates, the excitatory synaptic drive for inducing the spinal CPG can originate from either supraspinal glutamatergic inputs or from within the spinal cord2,3. Here we identify a spinal input to the CPG that drives spontaneous locomotion using a combination of intersectional gene expression and optogenetics4 in zebrafish larvae. The photo-stimulation of one specific cell type was sufficient to induce a symmetrical tail beating sequence that mimics spontaneous slow forward swimming. This neuron is the Kolmer–Agduhr cell5, which extends cilia into the central cerebrospinal-fluid-containing canal of the spinal cord and has an ipsilateral ascending axon that terminates in a series of consecutive segments6. Genetically silencing Kolmer–Agduhr cells reduced the frequency of spontaneous free swimming, indicating that activity of Kolmer–Agduhr cells provides necessary tone for spontaneous forward swimming. Kolmer–Agduhr cells have been known for over 75 years, but their function has been mysterious. Our results reveal that during early development in zebrafish these cells provide a positive drive to the spinal CPG for spontaneous locomotion.