Brainstem Circuits for Locomotion

Leiras, Roberto; Cregg, Jared M.; Kiehn, Ole

doi:10.1146/annurev-neuro-082321-025137

Cited by 71 publications

(61 citation statements)

References 150 publications

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“…A longstanding question in neuroscience is how neural circuits flexibly control the limbs during behaviors like walking and reaching. In vertebrate animals, enormous effort has been dedicated to understanding cortical and subcortical circuits that plan movements and issue descending commands (Arber and Costa, 2022; Inagaki et al, 2022; Leiras et al, 2022). There is also an extensive body of literature on the physiology and function of motor neurons (MNs) that directly control muscle activity (Binder et al, 2020; Kernell, 2006).…”

Section: Introductionmentioning

confidence: 99%

Tools for connectomic reconstruction and analysis of a femaleDrosophilaventral nerve cord

Azevedo

Lesser

Mark

et al. 2022

Preprint

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Like the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we applied automated tools for electron microscopy (EM) volume alignment, neuron reconstruction, and synapse prediction to create a draft connectome of theDrosophilaVNC. To interpret the VNC connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and x-ray holographic nano-tomography volumes of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings with the middle and front legs during escape takeoff. We provide the draft VNC connectome and motor neuron atlas, along with tools for programmatic and interactive access, as community resources.

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Section: Introductionmentioning

confidence: 99%

Tools for connectomic reconstruction and analysis of a femaleDrosophilaventral nerve cord

Azevedo

Lesser

Mark

et al. 2022

Preprint

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“…The executing locomotor circuits that control coordinated muscle activity are localized in the spinal cord [1][2][3] , whereas the commands for initiating locomotion reside in supraspinal structures, including the mesencephalic locomotor region (MLR), which control the start and speed of locomotion [4][5][6][7][8][9][10][11] . Reticulospinal command neurons integrate the signals from the MLR before they activate spinal executing locomotor circuits 5,[11][12][13][14] .…”

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confidence: 99%

Deconstructing the modular organization and real-time dynamics of mammalian spinal locomotor networks

2023

Self Cite

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Locomotion empowers animals to move. Locomotor-initiating signals from the brain are funneled through descending neurons in the brainstem that act directly on spinal locomotor circuits. Little is known in mammals about which spinal circuits are targeted by the command and how this command is transformed into rhythmicity in the cord. Here we address these questions leveraging a mouse brainstem-spinal cord preparation from either sex that allows locating the locomotor command neurons with simultaneous Ca2+ imaging of spinal neurons. We show that a restricted brainstem area – encompassing the lateral paragigantocellular nucleus (LPGi) and caudal ventrolateral reticular nucleus (CVL) – contains glutamatergic neurons which directly initiate locomotion. Ca2+ imaging captures the direct LPGi/CVL locomotor initiating command in the spinal cord and visualizes spinal glutamatergic modules that execute the descending command and its transformation into rhythmic locomotor activity. Inhibitory spinal networks are recruited in a distinctly different pattern. Our study uncovers the principal logic of how spinal circuits implement the locomotor command using a distinct modular organization.

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“…Direct ascending proprioceptive afferents convey in the cuneate and gracile nuclei of the dorsal column. In the cat, it has been shown that intra‐cuneate networks are responsible for the potentiation of proprioceptive feedback from the forelimb and that cuneate cells project to the reticular formation and the mesencephalic locomotor region (Leiras et al., 2010), with both known to have key roles in the initiation, control and termination of locomotion (Caggiano et al., 2018; Cregg et al., 2020; Grillner & El Manira, 2020; Leiras et al., 2022). To further elucidate the specific roles of the aforementioned structures in the regulation of proprioceptive information during locomotion, additional experiments are certainly needed.…”

Section: Discussionmentioning

confidence: 99%

The brain integrates proprioceptive information to ensure robust locomotion

Santuz

Laflamme

Akay

2022

The Journal of Physiology

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Robust locomotion relies on information from proprioceptors: sensory organs that communicate the position of body parts to the spinal cord and brain. Proprioceptive circuits in the spinal cord are known to coarsely regulate locomotion in the presence of perturbations. Yet, the regulatory importance of the brain in maintaining robust locomotion remains less clear. Here, through mouse genetic studies and in vivo electrophysiology, we examined the role of the brain in integrating proprioceptive information during perturbed locomotion. The systemic removal of proprioceptors left the mice in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild‐type mice and characterised by longer and less accurate synergistic activation patterns. By contrast, after surgically interrupting the ascending proprioceptive projection to the brain through the dorsal column of the spinal cord, wild‐type mice showed normal walking behaviour, yet lost the ability to respond to external perturbations. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving robust, safe locomotion. Key points Whether brain integration of proprioceptive feedback is crucial for coping with perturbed locomotion is not clear. We showed a crucial role of the brain for responding to external perturbations and ensure robust locomotion. We used mouse genetics to remove proprioceptors and a spinal lesion model to interrupt the flow of proprioceptive information to the brain through the dorsal column in wild‐type animals. Using a custom‐built treadmill, we administered sudden and random mechanical perturbations to mice during walking. External perturbations affected locomotion in wild‐type mice similar to the absence of proprioceptors in genetically modified mice. Proprioceptive feedback from muscle spindles and Golgi tendon organs contributed to locomotor robustness. Wild‐type mice lost the ability to respond to external perturbations after interruption of the ascending proprioceptive projection to the brainstem.

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Brainstem Circuits for Locomotion

Cited by 71 publications

References 150 publications

Tools for connectomic reconstruction and analysis of a femaleDrosophilaventral nerve cord

Tools for connectomic reconstruction and analysis of a femaleDrosophilaventral nerve cord

Deconstructing the modular organization and real-time dynamics of mammalian spinal locomotor networks

The brain integrates proprioceptive information to ensure robust locomotion

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