The interdependence of excitation and inhibition for the control of dynamic breathing rhythms DOI Creative Commons
Nathan A. Baertsch, Hans Baertsch, Jan‐Marino Ramirez

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Feb. 20, 2018

The preBötzinger Complex (preBötC), a medullary network critical for breathing, relies on excitatory interneurons to generate the inspiratory rhythm. Yet, half of preBötC neurons are inhibitory, and role inhibition in rhythmogenesis remains controversial. Using optogenetics electrophysiology vitro vivo, we demonstrate that intrinsic excitability is reduced following large depolarizing bursts. This refractory period limits very slow breathing frequencies. Inhibition integrated within required prevent overexcitation neurons, thereby regulating allowing rapid breathing. In sensory feedback also regulates period, slowly mice with removed, activity but not excitatory, restores physiological We conclude excitation interdependent rhythm, because permits bursting by controlling properties neurons.

Language: Английский

Attractor and integrator networks in the brain DOI

Mikail Khona,

Ila Fiete

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(12), P. 744 - 766

Published: Nov. 3, 2022

Language: Английский

Citations

184
A harmonized atlas of mouse spinal cord cell types and their spatial organization DOI Creative Commons
D. Russ, Ryan B. Patterson Cross, Li Li

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Sept. 29, 2021

Abstract Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases mouse spinal cord have been published in recent years but not integrated together. Here, we generate an atlas types based on single-cell transcriptomic data, unifying available datasets into a common reference framework. We report hierarchical structure postnatal relationships, with location providing highest level organization, then neurotransmitter status, family, and finally, dozens refined populations. validate combinatorial marker code for each neuronal map their spatial distributions adult cord. also show complex lineage relationships among Additionally, develop open-source classifier, SeqSeek, to facilitate standardization identification. This work provides view types, gene expression signatures, organization.

Language: Английский

Citations

181
The neurons that restore walking after paralysis DOI Creative Commons
Claudia Kathe, Michael A. Skinnider, Thomas H. Hutson

et al.

Nature, Journal Year: 2022, Volume and Issue: 611(7936), P. 540 - 547

Published: Nov. 9, 2022

Abstract A spinal cord injury interrupts pathways from the brain and brainstem that project to lumbar cord, leading paralysis. Here we show spatiotemporal epidural electrical stimulation (EES) of 1–3 applied during neurorehabilitation 4,5 (EES REHAB ) restored walking in nine individuals with chronic injury. This recovery involved a reduction neuronal activity humans walking. We hypothesized this unexpected reflects activity-dependent selection specific subpopulations become essential for patient walk after To identify these putative neurons, modelled technological therapeutic features underlying EES mice. single-nucleus RNA sequencing 6–9 spatial transcriptomics 10,11 cords mice chart spatially resolved molecular atlas then employed cell type 12,13 prioritization neurons single population excitatory interneurons nested within intermediate laminae emerged. Although are not required before injury, demonstrate they following Augmenting phenocopied enabled by , whereas ablating them prevented occurs spontaneously moderate thus identified recovery-organizing subpopulation is necessary sufficient regain Moreover, our methodology establishes framework using cartography produce complex behaviours.

Language: Английский

Citations

177
Graded Arrays of Spinal and Supraspinal V2a Interneuron Subtypes Underlie Forelimb and Hindlimb Motor Control DOI Creative Commons
Marito Hayashi, Christopher A. Hinckley, Shawn P. Driscoll

et al.

Neuron, Journal Year: 2018, Volume and Issue: 97(4), P. 869 - 884.e5

Published: Feb. 1, 2018

The spinal cord contains neural networks that enable regionally distinct motor outputs along the body axis. Nevertheless, it remains unclear how segment-specific computations are processed because cardinal interneuron classes control neurons appear uniform at each level of cord. V2a interneurons essential to both forelimb and hindlimb movements, here we identify two major types emerge during development: type I marked by high Chx10 form recurrent with neighboring II downregulate project supraspinal structures. Types arrayed in counter-gradients, this network activates different patterns output cervical lumbar levels. Single-cell RNA sequencing (RNA-seq) revealed comprised multiple subtypes. Our findings uncover a molecular anatomical organization reminiscent orderly way divided into columns pools.

Language: Английский

Citations

172
Motor Neuron Susceptibility in ALS/FTD DOI Creative Commons
Audrey Ragagnin, Sina Shadfar, Marta Vidal

et al.

Frontiers in Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 27, 2019

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of both upper and lower motor neurons (MNs) in brain, brainstem spinal cord. The mechanisms leading to MN loss ALS are not fully understood. Importantly, reasons why MNs specifically targeted this disorder unclear, when proteins associated genetically or pathologically with expressed ubiquitously. Furthermore, themselves affected equally; specific subpopulations more susceptible than others animal models human patient tissues. Corticospinal somatic MNs, which innervate voluntary muscles, degenerate readily subgroups remain resistant degeneration, reflecting clinical manifestations ALS. In review, we discuss possible factors intrinsic that render them uniquely neurodegeneration We also speculate some vulnerable others, focussing on their molecular physiological properties. Finally, review anatomical network neuronal microenvironment as determinants subtype vulnerability hence progression

Language: Английский

Citations

172
Epidural stimulation of the cervical spinal cord for post-stroke upper-limb paresis DOI
Marc Powell, Nikhil Verma, Erynn Sorensen

et al.

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(3), P. 689 - 699

Published: Feb. 20, 2023

Language: Английский

Citations

107
Emergence of robust self-organized undulatory swimming based on local hydrodynamic force sensing DOI
Robin Thandiackal, Kamilo Melo, Laura Paez

et al.

Science Robotics, Journal Year: 2021, Volume and Issue: 6(57)

Published: Aug. 11, 2021

Undulatory swimming represents an ideal behavior to investigate locomotion control and the role of underlying central peripheral components in spinal cord. Many vertebrate swimmers have pattern generators local pressure-sensitive receptors that provide information about surrounding fluid. However, it remains difficult study experimentally how these sensors influence motor commands animals. Here, using a specifically designed robot captures essential animal neuromechanical system simulations, we tested hypothesis sensed hydrodynamic pressure forces can entrain body actuation through feedback loops. We found evidence this mechanism leads self-organized undulatory by providing intersegmental coordination oscillations. Swimming be redundantly induced mechanisms, show that, therefore, combination both mechanisms offers higher robustness against neural disruptions than any them alone, which potentially explains some vertebrates retain locomotor capabilities after cord lesions. These results broaden our understanding expand knowledge for design robust modular robots physically interact with environment.

Language: Английский

Citations

104
Brainstem Circuits for Locomotion DOI
Roberto Leiras, Jared M. Cregg, Ole Kiehn

et al.

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 63 - 85

Published: Jan. 5, 2022

Locomotion is a universal motor behavior that expressed as the output of many integrated brain functions. organized at several levels nervous system, with brainstem circuits acting gate between areas regulating innate, emotional, or motivational locomotion and executive spinal circuits. Here we review recent advances on involved in controlling locomotion. We describe how delineated command govern start, speed, stop, steering also discuss these pathways interface cord diverse important for context-specific selection A recurrent theme need to establish functional connectome from Finally, point unresolved issues concerning function locomotor control.

Language: Английский

Citations

91
Recovery of walking after paralysis by regenerating characterized neurons to their natural target region DOI
Jordan W. Squair, Marco Milano, Alexandra de Coucy

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6664), P. 1338 - 1345

Published: Sept. 21, 2023

Axon regeneration can be induced across anatomically complete spinal cord injury (SCI), but robust functional restoration has been elusive. Whether restoring neurological functions requires directed of axons from specific neuronal subpopulations to their natural target regions remains unclear. To address this question, we applied projection-specific and comparative single-nucleus RNA sequencing identify that restore walking after incomplete SCI. We show chemoattracting guiding the transected these neurons region led substantial recovery SCI in mice, whereas simply lesion had no effect. Thus, reestablishing projections characterized forms an essential part axon strategies aimed at lost functions.

Language: Английский

Citations

73
Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice DOI Creative Commons

Su Young Han,

Paul G. Morris, Jae-Chang Kim

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(1), P. 111914 - 111914

Published: Jan. 1, 2023

Language: Английский

Citations

68