Using mouse genetics to investigate supraspinal pathways of the brain important to locomotion

Roussel, Marie; Lemieux, Maxime; Bretzner, Frédéric

doi:10.1016/b978-0-12-816477-8.00012-0

Cited by 7 publications

(6 citation statements)

References 241 publications

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“…As discussed in the previous section, DSCAM exhibits locomotor deficits that are central in origin and might include a reorganization of brainstem networks. As recently described [76,[145][146][147], the medullary reticular formation is organized into discrete nuclei, with the gigantocellular reticular nucleus located along the rostrocaudal axis of the medulla and the lateral paragigantocellular nucleus located ventrally and laterally to the gigantocellular reticular nucleus in the caudal medulla (Figure 4A). Both nuclei appear to integrate and relay the command of supraspinal locomotor centers, such as the Mesencephalic Locomotor Region to the spinal locomotor circuit, through their reticulospinal pathways.…”

Section: Locomotor Brainstem Circuitssupporting

confidence: 53%

“…Kinematics and electromyographic recordings are currently used to investigate locomotor control: the footfall pattern can be analyzed to monitor interlimb coordination, whereas the angular excursion of limb joints can be analyzed to study intralimb coordination during the swing and stance phase of locomotion. To complement kinematic analyses, electromyographic recordings can detail the spatial and temporal recruitment of muscle activities at a higher resolution than kinematics [76]. Combining data on interlimb coordination and the duty cycle of the stance phase of loco-motion, it is then possible to characterize and identify walking vs. running gaits, as well as transition gaits [77].…”

Section: Intralimb and Interlimb Coordination And Gaitmentioning

confidence: 99%

“…Gait analysis can be useful for investigating the development and establishment of motor circuits underlying intralimb and interlimb coordination, as well as forelimbhindlimb coordination [76,77,87]. It is possible to get insights about the spinal cervical and lumbar locomotor circuits, their reciprocal interaction through propriospinal interneurons, and their modulation by peripheral inputs of primary sensory afferents and by supraspinal descending inputs of the brain upon genetic mutation.…”

Section: Forelimb and Hindlimb Locomotor Coordinationmentioning

confidence: 99%

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Role of DSCAM in the Development of Neural Control of Movement and Locomotion

Lemieux

Thiry

Laflamme

et al. 2021

IJMS

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Locomotion results in an alternance of flexor and extensor muscles between left and right limbs generated by motoneurons that are controlled by the spinal interneuronal circuit. This spinal locomotor circuit is modulated by sensory afferents, which relay proprioceptive and cutaneous inputs that inform the spatial position of limbs in space and potential contacts with our environment respectively, but also by supraspinal descending commands of the brain that allow us to navigate in complex environments, avoid obstacles, chase prey, or flee predators. Although signaling pathways are important in the establishment and maintenance of motor circuits, the role of DSCAM, a cell adherence molecule associated with Down syndrome, has only recently been investigated in the context of motor control and locomotion in the rodent. DSCAM is known to be involved in lamination and delamination, synaptic targeting, axonal guidance, dendritic and cell tiling, axonal fasciculation and branching, programmed cell death, and synaptogenesis, all of which can impact the establishment of motor circuits during development, but also their maintenance through adulthood. We discuss herein how DSCAM is important for proper motor coordination, especially for breathing and locomotion.

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Section: Locomotor Brainstem Circuitssupporting

confidence: 53%

Section: Intralimb and Interlimb Coordination And Gaitmentioning

confidence: 99%

Section: Forelimb and Hindlimb Locomotor Coordinationmentioning

confidence: 99%

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Role of DSCAM in the Development of Neural Control of Movement and Locomotion

Lemieux

Thiry

Laflamme

et al. 2021

IJMS

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“…Despite very little understanding of the neural brainstem networks underlying locomotion (Ausborn et al, 2019; Roussel et al, 2020), recent optogenetic studies have shown that photo-stimulation of glutamatergic neurons of the LPGi modulate locomotor rhythm (Capelli et al, 2017), presumably by relaying glutamatergic inputs of the CnF, whereas photoactivation of glutamatergic or glutamatergic V2a (Lhx3/Chx10) expressing neurons of the Gi reset locomotor rhythm and induce locomotor arrests (Bouvier et al, 2015; Cregg et al, 2020; Lemieux and Bretzner, 2019; Usseglio et al, 2020), presumably by relaying glutamatergic inputs of the PPN. Further studies are needed to genetically dissect the neural mechanisms of these medullary nuclei to motor recovery after SCI.…”

Section: Discussionmentioning

confidence: 99%

Functional Contribution of Mesencephalic Locomotor Region Nuclei to Locomotor Recovery After Spinal Cord Injury

Roussel

Lafrance-Zoubga

Josset

et al. 2022

Preprint

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Spinal cord injury (SCI) results in a disruption of information between the brain and the spinal locomotor circuit. Although the spinal cord contains all the neural circuits to generate locomotion, people with SCI are unable to walk due to the absence of descending commands from the brain. Electrical stimulation of supraspinal locomotor centers, such as the Mesencephalic Locomotor Region (MLR), can promote locomotor recovery in acute and chronic SCI rodent models. Although clinical trials are currently underway in SCI patients, there is still debate about the organization of this supraspinal locomotor center and which anatomical correlate of the MLR should be targeted to promote functional recovery. Combining kinematics, electromyographic recordings, anatomical analysis, and mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus contribute to locomotor recovery by enhancing motor efficacy in flexor and extensor hindlimb muscles, and by increasing locomotor rhythm and speed on a treadmill, over ground, and during swimming in mice with chronic SCI. In contrast, glutamatergic neurons of the pedunculopontine nucleus slow down locomotion. Therefore, our study identifies the cuneiform nucleus and its glutamatergic neurons as a therapeutical target to improve locomotor recovery in patients living with SCI.One Sentence SummaryGlutamatergic neurons of the mesencephalic locomotor region contribute to spontaneous locomotor recovery following spinal cord injury and selective activation of a discrete glutamatergic subpopulation in this region can further improve functional outcome in chronic spinal cord injury.

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“…More motor neurons become involved in subsequent stages, and pTDP-43 aggregates do not remain confined to α-motor neurons. For example, nerve cells in the parvocellular red nucleus [65] that project to its magnocellular part and terminate in the inferior olive become involved (stage 2). The projections to the parvocellular red nucleus, which is the predominant portion of the red nucleus in humans, receives strong afferents from the cerebral cortex supplied by an independent corticorubral pathway [66].…”

Section: Neuropathological Staging Of Sporadic Amyotrophic Lateral Sc...mentioning

confidence: 99%

Neuropathology and neuroanatomy of TDP-43 amyotrophic lateral sclerosis

Tredici

Braak²

2022

Current Opinion in Neurology

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Purpose of reviewIntracellular inclusions consisting of the abnormal TDP-43 protein and its nucleocytoplasmic mislocalization in selected cell types are hallmark pathological features of sALS. Descriptive (histological, morphological), anatomical, and molecular studies all have improved our understanding of the neuropathology of sporadic amyotrophic lateral sclerosis (sALS). This review highlights some of the latest developments in the field. Recent findingsIncreasing evidence exists from experimental models for the prion-like nature of abnormal TDP-43, including a strain-effect, and with the help of neuroimaging-based studies, for spreading of disease along corticofugal connectivities in sALS. Progress has also been made with respect to finding and establishing reliable biomarkers (neurofilament levels, diffusor tensor imaging).

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Using mouse genetics to investigate supraspinal pathways of the brain important to locomotion

Cited by 7 publications

References 241 publications

Role of DSCAM in the Development of Neural Control of Movement and Locomotion

Role of DSCAM in the Development of Neural Control of Movement and Locomotion

Functional Contribution of Mesencephalic Locomotor Region Nuclei to Locomotor Recovery After Spinal Cord Injury

Neuropathology and neuroanatomy of TDP-43 amyotrophic lateral sclerosis

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