Spinal V2b neurons reveal a role for ipsilateral inhibition in speed control

Abstract

10The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, 11 models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal 12 alternation between left and right sides or flexors and extensors. However, recent work has 13shown that inhibition also increases coincident with excitation during contraction. Here, using 14 larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-15 extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines 16 we define two stable subclasses with distinct neurotransmitter and morphological properties. 17These two V2b subclasses make direct synapses onto motor neurons with differential targeting to 18 slower and faster circuits. In vivo, optogenetic suppression of V2b activity leads to increases in 19 locomotor speed. We conclude that V2b neurons exert speed-specific influence over axial motor 20 circuits throughout the rostrocaudal axis. Together, these results indicate a new role for 21 ipsilateral inhibition in speed control. 22 46In-phase inhibition is thought to derive from two spinal interneuron classes, the V1 and V2b 47 populations. The V1 population includes Renshaw cells [15, 16], which provide recurrent 48 inhibition onto motor neurons with potentially significant shunting effects [17]. To date, most 49 analysis of drive from V2b neurons has focused on the shared contributions of V1s and V2bs to 50 reciprocal inhibition governing flexor/extensor alternation in limbed animals [18][19][20]. However, 51 this does not shed light on potential functions of ipsilateral inhibition in gain control for 52 regulation of motor neuron firing during contraction, as opposed to suppression of motor neuron 53 firing during extension. 54 55In-phase inhibition increases in amplitude for faster locomotor movements [10] suggesting a 56 potential role in speed control. Here we investigated whether V2b neurons could indeed provide 57 direct inhibition to motor neurons for speed control, taking advantage of the speed-dependent 58 organization of zebrafish motor circuits [21][22][23]. V2b neurons are good candidates for in-phase 59 gain control because they are exclusively inhibitory in mouse and zebrafish [24] with ipsilateral, 60 descending axons within the spinal cord [18, 25]. They arise from a final progenitor division that 61 produces pairs of V2a and V2b neurons [26]. Given the role of V2a neurons in triggering motor 62 output [27, 28], particularly through speed-specific circuits for titrating levels of motor excitation 63[4, 29-31], it seems plausible that their sister V2b neurons exert an opposing, inhibitory role in 64 speed control. However, the V2b class has not been well characterized at anatomical or 65 neurochemical levels outside of very early development. 66 67 5Here, we define two subclasses of V2b neurons in larval zebrafish based on differential 68 transmitter expression and anatomy, and further show that these neurons directly inhibit a...

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A size principle for recruitment of Drosophila leg motor neurons

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