A Single Cell Atlas of Spared Tissue Below a Spinal Cord Injury Reveals Cellular Mechanisms of Repair DOI Creative Commons
Kaya J.E. Matson, D. Russ, Claudia Kathe

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2021, Номер unknown

Опубликована: Апрель 29, 2021

Abstract After spinal cord injury (SCI), the “spared” tissue below lesion contains undamaged cells that could support or augment recovery, but targeting these requires a clearer understanding of their responses and capacity for repair. Here, we used single nucleus sequencing to profile how each cell type in lumbar changes over time after thoracic injury. We present an atlas dynamic explore two unexpected findings. Amongst neurons, rare types expressed molecular signature regeneration amongst microglia, identified population “trauma associated microglia” (TAM). These TAM were white matter near degenerating axons trophic factors Igf1 Spp1 (OPN). Viral over-expression (OPN) expanded promoted clearance myelin debris. findings expose endogenous mechanisms repair spared neural tissue, uncovering potential candidates targeted therapy.

Язык: Английский

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion DOI Creative Commons
Sten Grillner, Abdeljabbar El Manira

Physiological Reviews, Год журнала: 2019, Номер 100(1), С. 271 - 320

Опубликована: Сен. 12, 2019

The vertebrate control of locomotion involves all levels the nervous system from cortex to spinal cord. Here, we aim cover main aspects this complex behavior, operation microcircuits in cord systems and behavioral extend mammalian basic undulatory movements lamprey fish. cellular basis propulsion represents core system, it central pattern generator networks (CPGs) controlling timing different muscles, sensory compensation for perturbations, brain stem command level activity CPGs speed locomotion. forebrain particular basal ganglia are involved determining which motor programs should be recruited at a given point time can both initiate stop locomotor activity. propulsive needs integrated with postural maintain body orientation. Moreover, need steered so that subject approaches goal episode, or avoids colliding elements environment simply escapes high speed. These will covered review.

Язык: Английский

Процитировано

434

Homeobox genes and the specification of neuronal identity DOI
Oliver Hobert

Nature reviews. Neuroscience, Год журнала: 2021, Номер 22(10), С. 627 - 636

Опубликована: Авг. 26, 2021

Язык: Английский

Процитировано

92

Multiple Rhythm-Generating Circuits Act in Tandem with Pacemaker Properties to Control the Start and Speed of Locomotion DOI Creative Commons
Jianren Song, Irene Pallucchi, Jessica Ausborn

и другие.

Neuron, Год журнала: 2020, Номер 105(6), С. 1048 - 1061.e4

Опубликована: Янв. 22, 2020

Язык: Английский

Процитировано

73

Single cell atlas of spinal cord injury in mice reveals a pro-regenerative signature in spinocerebellar neurons DOI Creative Commons
Kaya J.E. Matson, D. Russ, Claudia Kathe

и другие.

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Сен. 26, 2022

Abstract After spinal cord injury, tissue distal to the lesion contains undamaged cells that could support or augment recovery. Targeting these requires a clearer understanding of their injury responses and capacity for repair. Here, we use single nucleus RNA sequencing profile how each cell type in lumbar changes after thoracic mice. We present an atlas dynamic across dozens types acute, subacute, chronically injured cord. Using this resource, find rare neurons express signature regeneration response including major population represent spinocerebellar projection neurons. characterize anatomically observed axonal sparing, outgrowth, remodeling cerebellum. Together, work provides key resource studying cellular uncovers spontaneous plasticity neurons, uncovering potential candidate targeted therapy.

Язык: Английский

Процитировано

66

Neurotransmitter phenotype switching by spinal excitatory interneurons regulates locomotor recovery after spinal cord injury DOI Creative Commons

Hannah Bertels,

Guillem Vicente-Ortiz,

Khadija El Kanbi

и другие.

Nature Neuroscience, Год журнала: 2022, Номер 25(5), С. 617 - 629

Опубликована: Май 1, 2022

Abstract Severe spinal cord injury in adults leads to irreversible paralysis below the lesion. However, adult rodents that received a complete thoracic lesion just after birth demonstrate proficient hindlimb locomotion without input from brain. How achieves such striking plasticity remains unknown. In this study, we found prompts neurotransmitter switching of spatially defined excitatory interneurons an inhibitory phenotype, promoting inhibition at synapses contacting motor neurons. contrast, neonatal maintains phenotype glutamatergic and causes synaptic sprouting facilitate excitation. Furthermore, genetic manipulation mimic observed abrogates autonomous locomotor functionality neonatally injured mice. comparison, attenuating improves capacity injury. Together, these data steers recovery

Язык: Английский

Процитировано

58

Spinal Interneurons: Diversity and Connectivity in Motor Control DOI Creative Commons
Mohini Sengupta, Martha W. Bagnall

Annual Review of Neuroscience, Год журнала: 2023, Номер 46(1), С. 79 - 99

Опубликована: Фев. 28, 2023

The spinal cord is home to the intrinsic networks for locomotion. An animal in which has been fully severed from brain can still produce rhythmic, patterned locomotor movements as long some excitatory drive provided, such physical, pharmacological, or electrical stimuli. Yet it remains a challenge define underlying circuitry that produces these because contains wide variety of neuron classes whose patterns interconnectivity are poorly understood. Computational models locomotion accordingly rely on untested assumptions about network element identity and connectivity. In this review, we consider neurons, their interconnectivity, significance circuit connections along axis cord. We suggest several lines analysis move toward definitive understanding network.

Язык: Английский

Процитировано

26

A dynamic role for dopamine receptors in the control of mammalian spinal networks DOI Creative Commons
Simon A. Sharples, Nicole E. Burma,

Joanna Borowska-Fielding

и другие.

Scientific Reports, Год журнала: 2020, Номер 10(1)

Опубликована: Окт. 2, 2020

Abstract Dopamine is well known to regulate movement through the differential control of direct and indirect pathways in striatum that express D 1 2 receptors respectively. The spinal cord also expresses all dopamine receptors; however, how specific network output mammals poorly understood. We explore receptor-specific mechanisms underlie dopaminergic neonatal mice during changes excitability. During spontaneous activity, which a characteristic developing networks operating low excitability state, we found primarily inhibitory. uncover an excitatory -mediated effect on motoneurons involves co-activation with receptors. Critically, these actions require higher concentrations dopamine; analysis neonates indicates endogenous levels are low. Because low, this pathway likely physiologically-silent at stage development. In contrast, inhibitory dopamine, physiological mediated by parallel activation , 3 4 α reproduced when increased blocking reuptake metabolism. provide evidence support dedicated components controlled reminiscent classic within striatum. These results indicate state important factor dictates therefore dose-dependent neuromodulators advances our understanding neural under dynamically changing

Язык: Английский

Процитировано

55

The CPGs for Limbed Locomotion–Facts and Fiction DOI Open Access
Sten Grillner, Alexander Kozlov

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(11), С. 5882 - 5882

Опубликована: Май 30, 2021

The neuronal networks that generate locomotion are well understood in swimming animals such as the lamprey, zebrafish and tadpole. controlling tetrapods remain, however, still enigmatic with an intricate motor pattern required for control of entire limb during support, lift off, flexion phase, most demandingly when makes contact ground again. It is clear inhibition occurs between bursts each step cycle produced by V2b V1 interneurons, a deletion these interneurons leads to synchronous flexor–extensor bursting. ability rhythmic bursting distributed over all segments comprising part central generator network (CPG). unclear how generated; Shox2, V2a HB9 do contribute. To deduce possible organization locomotor CPG, simulations have been elaborated. has simulated considerable detail composed unit burst generators; one group close synergistic muscle groups at joint. This model can reproduce complex constant phase shortened extensor speed increases. Moreover, versatile both forward backward locomotion.

Язык: Английский

Процитировано

53

The enteric nervous system of the C. elegans pharynx is specified by the Sine oculis-like homeobox gene ceh-34 DOI Creative Commons

Berta Vidal,

Burcu Gülez,

Wen Xi Cao

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Март 24, 2022

Overarching themes in the terminal differentiation of enteric nervous system, an autonomously acting unit animal systems, have so far eluded discovery. We describe here overall regulatory logic system nematode Caenorhabditis elegans that resides within foregut (pharynx) worm. A C. homolog Drosophila Sine oculis homeobox gene, ceh-34 , is expressed all 14 classes interconnected pharyngeal neurons from their birth throughout life time, but no other neuron type entire animal. Constitutive and temporally controlled removal shows required to initiate maintain type-specific program classes, including circuit assembly. Through additional genetic loss function analysis, we show each class, cooperates with different homeodomain transcription factors individuate distinct classes. Our analysis underscores critical role genes neuronal identity specification links them control assembly system. Together simplicity as well its by a homolog, our findings invite speculations about early evolution systems.

Язык: Английский

Процитировано

38

Spinal cords: Symphonies of interneurons across species DOI Creative Commons

Alexia C. Wilson,

Lora B. Sweeney

Frontiers in Neural Circuits, Год журнала: 2023, Номер 17

Опубликована: Апрель 26, 2023

Vertebrate movement is orchestrated by spinal inter- and motor neurons that, together with sensory cognitive input, produce dynamic behaviors. These behaviors vary from the simple undulatory swimming of fish larval aquatic species to highly coordinated running, reaching grasping mice, humans other mammals. This variation raises fundamental question how circuits have changed in register behavior. In simple, fish, exemplified lamprey, two broad classes interneurons shape neuron output: ipsilateral-projecting excitatory neurons, commissural-projecting inhibitory neurons. An additional class ipsilateral required generate escape swim behavior zebrafish tadpoles. limbed vertebrates, a more complex composition observed. this review, we provide evidence that elaboration correlates an increase specialization these three basic interneuron types into molecularly, anatomically, functionally distinct subpopulations. We summarize recent work linking movement-pattern generation across amphibians, reptiles, birds

Язык: Английский

Процитировано

21