Transformation of an early-established motor circuit during maturation in zebrafish

Complexity of modular neuromuscular control increases and variability decreases during human locomotor development

“…Work in animal models shows that the basic neural circuits underlying locomotor-like behavior are laid down in the spinal cord at early stages of development, well before birth 54,55 . However, they are then modified extensively over a prolonged postnatal period by experience, with spontaneous neural activity, sensory feedback, and supraspinal control playing a critical role in shaping progressively the locomotor function 24,40,41,56 . Similarly, developmental studies in humans show that locomotor-like behavior is present prior to and at birth 25,[32][33][34][35][36]42 , but the kinematic and kinetic features typical of mature locomotion are reached only after several years 57 .…”

“…The hypothesis that components of early-established motor circuits are substrative and retained in adults, but their connectivity undergoes major reconfiguration during maturation 34 is also supported by work on animal models 24 , 39 . Thus, while spinal motor circuits are established early during development allowing animals to generate a variety of movements prior to and at birth 25 , 40 , the activity of these motor circuits changes drastically during development 41 .…”

Mixed synapses reconcile violations of the size principle in zebrafish spinal cord

“…Mixed synapses formed by reticulospinal and propriospinal interneurons provide sources of excitation during locomotion in larval zebrafish ( Bhatt et al, 2007 ; Kimura et al, 2006 ; McLean et al, 2008 ; Menelaou and McLean, 2019 ; Pujala and Koyama, 2019 ; Wang and McLean, 2014 ). They also appear early in zebrafish embryos ( Miller et al, 2015 ; Saint-Amant and Drapeau, 2001 ) and persist into adulthood ( Pallucchi et al, 2022 ; Song et al, 2016 ). Thus, it is likely that gap junctions in mixed synapses impact electrophysiological assessments in zebrafish of all ages.…”

Unique advantages of zebrafish larvae as a model for spinal cord regeneration

“…An additional consideration supporting the use of the larval zebrafish model arises from the recent finding that there is a substantial reorganization of spinal motor circuits between larval and adult stages (Pallucchi et al, 2022 ). Because our understanding of zebrafish spinal circuitry primarily comes from studies using larvae, and due to the emerging importance of synaptic and modulatory neurotransmitters as pro-regenerative signals (Chang et al, 2021 ; Huang et al, 2021 ), our ability to accurately characterize the sources and targets underlying functional recovery after SCI may depend on performing future investigations at a stage before this reorganization occurs.…”

“…The patterning of the zebrafish spinal cord into progenitor domains arranged along the dorsoventral axis (Lewis and Eisen, 2003 ) occurs through signaling morphogen gradients that are established before 1 dpf (Bonner et al, 2008 ; Danesin et al, 2021 ), and shortly thereafter drive expression of the homeodomain transcription factors that define these domains (Gribble et al, 2007 ; Bonner et al, 2008 ; Lien et al, 2016 ). The identity and position of differentiated neuronal subtypes is largely established by 3 dpf (Seredick et al, 2012 ; Reimer et al, 2013 ; Lien et al, 2016 ; Ohnmacht et al, 2016 ; Andrzejczuk et al, 2018 ; England et al, 2020 ), and by 4 dpf these neurons are assembled into functional circuits required for the transition to a mature swimming pattern, increased locomotion, and the emergence of foraging behavior (Buss and Drapeau, 2001 ; Borla et al, 2002 ; Kokel et al, 2010 ; Menelaou and McLean, 2012 ; Kroll et al, 2021 ; Pallucchi et al, 2022 ). Ependymal radial glia (ERG), the resident neural progenitor cells of the zebrafish spinal cord (Briona and Dorsky, 2014a ; Hui et al, 2015 ), begin to establish characteristic marker expression and morphology at 2 dpf (Kim et al, 2008 ; Briona and Dorsky, 2014a ; Matsuoka et al, 2016 ), and subpopulations of ERG have become fate-restricted by 3 dpf (Ali et al, 2021 ).…”