Intrinsic brainstem circuits comprised of Chx10-expressing neurons contribute to reticulospinal output in mice

Chopek, Jeremy W.; Zhang, Ying; Brownstone, Robert M.

doi:10.1152/jn.00322.2021

Cited by 9 publications

(7 citation statements)

References 59 publications

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“…Thus, an alternative model for changes in locomotion directionality could be that short-latency head turning combined with a following speed decrease allows body reorientation to align with head position. Moreover, a recent study showed the existence of locally projecting Chx10-Gi neurons with distinct in vitro physiological properties and connected to the long-range projecting Chx10-Gi population 21 . The in vivo function of these neurons is however not known.…”

Section: Locomotion: Speed and Directionmentioning

confidence: 99%

Networking brainstem and basal ganglia circuits for movement

2022

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Execution and learning of diverse movements involve neuronal networks distributed throughout the nervous system. Brainstem and basal ganglia are key for processing motor information. Both harbor functionally-specialized populations stratified based on axonal projections, synaptic inputs and gene expression, revealing a correspondence between circuit anatomy and function at a high level of granularity. Neuronal populations within both structures form multi-step processing chains dedicated to the execution of specific movements. However, the connectivity and communication between these two structures is only just beginning to be revealed. Brainstem and basal ganglia are also embedded into wider networks, and systems-level loops. Important networking components include broadcasting neurons in cortex, cerebellar output neurons, and midbrain dopaminergic neurons. Action-specific circuits can be enhanced, vetoed, work in synergy or competition with others or undergo plasticity to allow for adaptive behavior. We propose that this highly specific organization of circuits in the motor system is a core ingredient for supporting behavioral specificity, and at the same time providing an adequate substrate for behavioral flexibility.

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Section: Locomotion: Speed and Directionmentioning

confidence: 99%

Networking brainstem and basal ganglia circuits for movement

2022

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“…Given that neuroanatomical changes are unlikely to occur within a week, the most likely scenario is that spared reticulospinal synapses might have undergone homeostatic plasticity 26 , 27 by enhancing their descending drive during the acute SCI phase. Because of a reciprocal connectivity between reticulospinal neurons and reticular interneurons within the medullary reticular formation 28 , synaptic and intrinsic plasticity could also occur at the supraspinal level. In addition to synaptic plasticity of reticulospinal pathways during the chronic phase, potentiation or recovery of motor responses likely also depend on neuroanatomical plasticity 13 , 14 , 29 as well as on a higher intrinsic excitability of the spinal locomotor network 30 .…”

Section: Discussionmentioning

confidence: 99%

Functional plasticity of glutamatergic neurons of medullary reticular nuclei after spinal cord injury in mice

Lemieux,

Karimi,

Bretzner

2024

Nat Commun

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Spinal cord injury disrupts the descending command from the brain and causes a range of motor deficits. Here, we use optogenetic tools to investigate the functional plasticity of the glutamatergic reticulospinal drive of the medullary reticular formation after a lateral thoracic hemisection in female mice. Sites evoking stronger excitatory descending drive in intact conditions are the most impaired after injury, whereas those associated with a weaker drive are potentiated. After lesion, pro- and anti-locomotor activities (that is, initiation/acceleration versus stop/deceleration) are overall preserved. Activating the descending reticulospinal drive improves stepping ability on a flat surface of chronically impaired injured mice, and its priming enhances recovery of skilled locomotion on a horizontal ladder. This study highlights the resilience and capacity for reorganization of the glutamatergic reticulospinal command after injury, along with its suitability as a therapeutical target to promote functional recovery.

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“…In contrast to efferents from hotspots, projections from "off" sites reached lumbar spinal sites with variable patterns and density while ascending projections from dorsal "off" sites were robust, particularly for the inhibitory system. Our study did not probe whether the heterogeneous "off" sites primarily serve other motor and non-motor functions (50,51) or modulate local interneurons that promote non-specific reticulospinal activation (52). Much remains unknown about the interplay between descending, local and ascending mRF circuits in integrating centrally-driven motor commands and conveying a unified response to spinal circuits with supraspinal feedforward and feedback mechanisms serving well-integrated motor function.…”

Section: Discrete Mrf Sites Serve Distinct Walking Stylesmentioning

confidence: 95%

Contrasting walking styles map to discrete neural substrates in the mouse brainstem

Worley

Kirby

Luks

et al. 2023

Preprint

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Walking is a slow gait which is particularly adaptable to meet internal or external needs and is prone to maladaptive alterations that lead to gait disorders. Alterations can affect speed, but also style (the way one walks). While slowed speed may signify the presence of a problem, style represents the hallmark essential for clinical classification of gait disorders. However, it has been challenging to objectively capture key stylistic features while uncovering neural substrates driving these features. Here we revealed brainstem hotspots that drive strikingly different walking styles by employing an unbiased mapping assay that combines quantitative walking signatures with focal, cell type specific activation. We found that activation of inhibitory neurons that mapped to the ventromedial caudal pons induced slow motion-like style. Activation of excitatory neurons that mapped to the ventromedial upper medulla induced shuffle-like style. Contrasting shifts in walking signatures distinguished these styles. Activation of inhibitory and excitatory neurons outside these territories or of serotonergic neurons modulated walking speed, but without walking signature shifts. Consistent with their contrasting modulatory actions, hotspots for slow-motion and shuffle-like gaits preferentially innervated different substrates. These findings lay the basis for new avenues to study mechanisms underlying (mal)adaptive walking styles and gait disorders.

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Intrinsic brainstem circuits comprised of Chx10-expressing neurons contribute to reticulospinal output in mice

Cited by 9 publications

References 59 publications

Networking brainstem and basal ganglia circuits for movement

Networking brainstem and basal ganglia circuits for movement

Functional plasticity of glutamatergic neurons of medullary reticular nuclei after spinal cord injury in mice

Contrasting walking styles map to discrete neural substrates in the mouse brainstem

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