Biology subjects

Bagnall, M. W.

Publications and source records attributed to Bagnall, M. W..

8 recordsLinked to original sources

bioRxiv2026

Spinal V2a neurons support locomotor propagation via long-range connectivity

The spinal cord contains a diverse set of neurons whose activity is vital for motor control. Despite the importance of these spinal interneurons in network models of locomotion, their circuitry remains poorly understood. We quantified the synaptic output of V2a (vsx2+) interneurons, a glutamatergic population implicated in control of locomotor speed, rhythm generation, and recovery from injury, using the larval zebrafish. Surprisingly, we found that the majority of monosynaptic output from V2a neurons occurs onto motor and premotor targets at long ranges, in contrast to models that posit V2a neurons as the source of recurrent local excitation. Focal loss of V2a neurons impairs long-range propagation of locomotor output, but not local rhythm generation, in accordance with their long-range connectivity. Our results position V2a neurons as major mediators of locomotor propagation and long-range coordination in the spinal cord.

neuroscience↗

bioRxiv2022

Neuronal birthdate reveals topography in a vestibular brainstem circuit for gaze stabilization

Across the nervous system, neurons with similar attributes are topographically organized. This topography reflects developmental pressures. Oddly, vestibular (balance) nuclei are thought to be disorganized. By measuring activity in birthdated neurons, we revealed a functional map within the central vestibular projection nucleus that stabilizes gaze in the larval zebrafish. We first discovered that both somatic position and stimulus selectivity follow projection neuron birthdate. Next, with electron microscopy and loss-of-function assays, we found that patterns of peripheral innervation to projection neurons were similarly organized by birthdate. Lastly, birthdate revealed spatial patterns of axonal arborization and synapse formation to projection neuron outputs. Collectively, we find that development reveals previously hidden organization to the input, processing, and output layers of a highly-conserved vertebrate sensorimotor circuit. The spatial and temporal attributes we uncover constrain the developmental mechanisms that may specify the fate, function, and organization of vestibulo-ocular reflex neurons. More broadly, our data suggest that, like invertebrates, temporal mechanisms may assemble vertebrate sensorimotor architecture.

neuroscience↗

bioRxiv2022

Clonally related, Notch-differentiated spinal neurons integrate into distinct circuits

Shared lineage has diverse effects on patterns of neuronal connectivity. In mammalian cortex, excitatory sister neurons assemble into shared microcircuits, whereas throughout the Drosophila nervous system, Notch-differentiated sister neurons diverge into distinct circuits. Notch-differentiated sister neurons have been observed in vertebrate spinal cord and cerebellum, but whether they integrate into shared or distinct circuits remains unknown. Here we evaluate the connectivity between sister V2a/b neurons in the zebrafish spinal cord. Using an in vivo labeling approach, we identified pairs of sister V2a/b neurons born from individual Vsx1+ progenitors and observed that they have similar axonal trajectories and proximal somata. However, paired whole-cell electrophysiology and optogenetics revealed that sister V2a/b neurons receive input from distinct presynaptic sources, do not communicate with each other, and connect to largely distinct targets. These results resemble the divergent connectivity in Drosophila and represent the first evidence of Notch-differentiated circuit integration in a vertebrate system.

neuroscience↗

bioRxiv2022

V2b neurons act via multiple targets in spinal motor networks

Within the spinal cord, interneurons shape motor neuron activity. These interneurons can project over long distances in the longitudinal axis, but systematic mapping of their connectivity has been limited. In this study, using larval zebrafish, we mapped local and long-range connectivity of a cardinal spinal population, the Gata3+ V2b class. V2b neurons are inhibitory and project ipsilateral, descending axons. We show that V2b neurons are active during fictive swimming, slightly leading the motor burst. Via optogenetic mapping of output in the rostrocaudal axis, we demonstrate that V2b neurons robustly inhibit motor neurons and other major spinal interneuron classes, including V2a, V1, commissural neurons and other V2b neurons. V2b inhibition is patterned along the rostrocaudal axis, providing long-range inhibition to motor and V2a neurons but more localized innervation of the V1 class. Furthermore, these results provide the first demonstration of reciprocal V1/V2b inhibition in axial circuits, potentially representing an ancestral motif of the limb control network.

neuroscience↗

bioRxiv2021

The organization of the gravity-sensing system in zebrafish

Motor circuits develop in sequence from those governing fast movements to those governing slow. Here we examine whether upstream sensory circuits are organized by similar principles. Using serial-section electron microscopy in larval zebrafish, we generated a complete map of the gravity-sensing (utricular) system spanning from the inner ear to the brainstem. We find that both sensory tuning and developmental sequence are organizing principles of vestibular topography. Patterned rostrocaudal innervation from hair cells to afferents creates an anatomically inferred directional tuning map in the utricular ganglion, forming segregated pathways for rostral and caudal tilt. Furthermore, the mediolateral axis of the ganglion is linked to both developmental sequence and neuronal temporal dynamics. Early-born pathways carrying phasic information preferentially excite fast escape circuits, whereas later-born pathways carrying tonic signals excite slower postural and oculomotor circuits. These results demonstrate that vestibular circuits are organized by tuning direction and dynamics, aligning them with downstream motor circuits and behaviors.

neuroscience↗

bioRxiv2021

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

Rostro-caudal coordination of spinal motor output is essential for locomotion. Most spinal interneurons project axons longitudinally to govern locomotor output, yet their connectivity along this axis remains unclear. In this study, we use larval zebrafish to map synaptic outputs of a major inhibitory population, V1 (Eng1+) neurons, which are implicated in dual sensory and motor functions. We find that V1 neurons exhibit long axons extending rostrally and exclusively ipsilaterally for an average of 6 spinal segments; however, they do not connect uniformly with their post-synaptic targets along the entire length of their axon. Locally, V1 neurons inhibit motor neurons (both fast and slow) and other premotor targets including V2a, V2b and commissural pre-motor neurons. In contrast, V1 neurons make robust inhibitory contacts throughout the rostral extent of their axonal projections onto a dorsal horn sensory population, the Commissural Primary Ascending neurons (CoPAs). In a computational model of the ipsilateral spinal network, we show that this pattern of short range V1 inhibition to motor and premotor neurons is crucial for coordinated rostro-caudal propagation of the locomotor wave. We conclude that spinal network architecture in the longitudinal axis can vary dramatically, with differentially targeted local and distal connections, yielding important consequences for function.

neuroscience↗

bioRxiv2020

Central vestibular tuning arises from patterned convergence of otolith afferents

As sensory information moves through the brain, higher-order areas exhibit more complex tuning than lower areas. Though models predict this complexity is due to convergent inputs from neurons with diverse response properties, in most vertebrate systems convergence has only been inferred rather than tested directly. Here we measure sensory computations in zebrafish vestibular neurons across multiple axes in vivo. We establish that whole-cell physiological recordings reveal tuning of individual vestibular afferent inputs and their postsynaptic targets. An independent approach, serial section electron microscopy, supports the inferred connectivity. We find that afferents with similar or differing preferred directions converge on central vestibular neurons, conferring more simple or complex tuning, respectively. Our data also resolve a long-standing contradiction between anatomical and physiological analyses by revealing that sensory responses are produced by sparse but powerful inputs from vestibular afferents. Together these results provide a direct, quantifiable demonstration of feedforward input convergence in vivo.

neuroscience↗

bioRxiv2019

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

The spinal cord contains a diverse array of interneurons that govern motor output. Traditionally, models of spinal circuits have emphasized the role of inhibition in enforcing reciprocal alternation between left and right sides or flexors and extensors. However, recent work has shown that inhibition also increases coincident with excitation during contraction. Here, using larval zebrafish, we investigate the V2b (Gata3+) class of neurons, which contribute to flexor-extensor alternation but are otherwise poorly understood. Using newly generated transgenic lines we define two stable subclasses with distinct neurotransmitter and morphological properties. These two V2b subclasses make direct synapses onto motor neurons with differential targeting to slower and faster circuits. In vivo, optogenetic suppression of V2b activity leads to increases in locomotor speed. We conclude that V2b neurons exert speed-specific influence over axial motor circuits throughout the rostrocaudal axis. Together, these results indicate a new role for ipsilateral inhibition in speed control.

neuroscience↗