Functional Diversity of Glycinergic Commissural Inhibitory Neurons in Larval Zebrafish

Abstract

Graphical Abstract Highlights d dI6dmrt3a and V0d neurons are commissural inhibitory neurons in zebrafish d dI6dmrt3a and V0d neurons are cooperatively involved in leftright alternation d dI6dmrt3a and V0d neurons are recruited at different frequencies of swimming d Ablation of dI6dmrt3a neurons impairs regular left-right alternation SUMMARY Commissural inhibitory neurons in the spinal cord of aquatic vertebrates coordinate left-right body alternation during swimming.Their developmental origin, however, has been elusive. We investigate this by comparing the anatomy and function of two commissural inhibitory neuron types, dI6dmrt3a and V0d, derived from the pd6 and p0 progenitor domains, respectively. We find that both of these commissural neuron types have monosynaptic, inhibitory connections to neuronal populations active during fictive swimming, supporting their role in providing inhibition to the contralateral side. V0d neurons tend to fire during faster and stronger movements, while dI6dmrt3a neurons tend to fire more consistently during normal fictive swimming. Ablation of dI6dmrt3a neurons leads to an impairment of left-right alternating activity through abnormal co-activation of ventral root neurons on both sides of the spinal cord. Our results suggest that dI6dmrt3a and V0d commissural inhibitory neurons synergistically provide inhibition to the opposite side across different swimming behaviors.

A spinal organ of proprioception for integrated motor action feedback

“…Conversely, the gene profile of single glyt2 + /dbx1b + neurons collected from the gray matter overlapped mostly with n 2 ( Figure 4F). The latter neurons correspond to the V0d interneuron population described previously in this zebrafish line (Satou et al, 2012(Satou et al, , 2020. We therefore performed a more detailed analysis of n 1 corresponding to the lateral neurons of the spinal enlargements.…”

“…A servomechanism for efficient locomotor behavior Next we examined whether the movement-encoded inhibitory feedback signal from ILP neurons is integrated in the central locomotor network. Our analysis focused on three core components of the zebrafish locomotor network: motor neurons (Ampatzis et al, 2013;Gabriel et al, 2011;Song et al, 2016), rhythm-generating excitatory V2a interneurons (Ampatzis et al, 2014;Ausborn et al, 2012;Ljunggren et al, 2014;Eklö f-Ljunggren et al, 2012;Song et al, 2018Song et al, , 2020, and left-right-coordinating inhibitory V0d interneurons (Satou et al, 2020), which were recorded during movement-induced activation of ILP neurons in the isolated spinal cord. In motor neurons, no response was induced by bending of the spinal cord in either direction ( Figure 7A).…”

“…For targeted recordings, intraspinal proprioceptors and V0d interneurons were labeled in Tg(glyt2,dbx:GFP) zebrafish (Satou et al, 2012(Satou et al, , 2020; V2a interneurons were labeled in Tg(Chx10:GFP) zebrafish (Ampatzis et al, 2014;Ausborn et al, 2012;Kimura et al, 2006;Song et al, 2018Song et al, , 2020; and motor neurons were back-labeled by injecting dextran dye into the muscles (Ampatzis et al, 2013;Gabriel et al, 2009Gabriel et al, , 2011. All recordings were performed using the whole-cell patch-clamp technique.…”

Spinal V1 neurons inhibit motor targets locally and sensory targets distally to coordinate locomotion

“…We considered the possibility that as V1 axons ascend and travel dorsally, they connect targeted ventral horn commissurally projecting neurons that are likely dI6/V0 identity. These neurons comprise both inhibitory and excitatory [52][53][54] subsets but are characterized by a common morphological motif: a commissural, bifurcating axonal trajectory 52,53 . We utilized this distinct morphology to categorize these neurons as Commissural Pre-motor (CoPr) neurons.…”

Induction of Ventral Spinal V0 Interneurons from Mouse Embryonic Stem Cells

“…Genetic ablation studies in mice showed that the two major subclasses are recruited in a frequency-dependent manner during locomotion; the inhibitory V0D INs are more active at low speeds and the excitatory V0V interneurons at higher frequencies [2]. However, a recent study in larval zebrafish showed that, in contrast to mice, V0D INs are important at higher frequencies [7]. Much remains to fully understand and characterize V0 IN subtypes and their role in locomotor circuits.…”