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| Open AccessRegulation of coordinated muscular relaxation in Drosophila larvae by a pattern-regulating intersegmental circuit
Patterned movements in animals are achieved through combinations of contraction and delayed relaxation of muscles. Here, the authors identify a class of cholinergic higher-order premotor interneurons that regulates muscular relaxation during backward locomotion of Drosophila larvae.
- Atsuki Hiramoto
- , Julius Jonaitis
- & Akinao Nose
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| Open AccessSingle nucleus RNA-sequencing defines unexpected diversity of cholinergic neuron types in the adult mouse spinal cord
The full heterogeneity and different functional roles of cholinergic neurons in the adult spinal cord remain to be defined. Here the authors develop a targeted single nuclear RNA sequencing approach and use it to identify an array of cholinergic interneurons, as well as visceral and skeletal motor neurons.
- Mor R. Alkaslasi
- , Zoe E. Piccus
- & Claire E. Le Pichon
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| Open AccessRecruitment of upper-limb motoneurons with epidural electrical stimulation of the cervical spinal cord
The efficacy of epidural electrical stimulation (EES) to engage arm muscles and improve movement after spinal cord injury is still unclear. Here, the authors investigated how EES can recruit upper-limb motor neurons by combining computational modelling with experiments in non-human primates.
- Nathan Greiner
- , Beatrice Barra
- & Marco Capogrosso
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Article
| Open AccessRetromer stabilization results in neuroprotection in a model of Amyotrophic Lateral Sclerosis
ALS is a neurodegenerative disease characterized by loss of motor neurons. Here, the authors showed that reduced levels of the VSP35 subunit in the retromer complex is a conserved ALS feature and identified a new lead compound increasing retromer stability ameliorating the disease phenotype.
- Luca Muzio
- , Riccardo Sirtori
- & Gianvito Martino
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| Open AccessInformation-based centralization of locomotion in animals and robots
Model-based centralization schemes, though able to quantify locomotion control in animals and bio-inspired robots, are limited to specific systems. Here, the authors report a generalized information-based centralization scheme that unifies existing models and can be applied to different systems.
- Izaak D. Neveln
- , Amoolya Tirumalai
- & Simon Sponberg
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| Open AccessIdentification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies
The wiring of peripheral neural circuits that regulate heart rate is poorly understood. In this study, authors used tissue clearing for high-resolution characterization of nerves in the heart in 3D and transgenic and novel viral vector approaches to identify peripheral parasympathetic and sympathetic neuronal populations involved in heart rate control in mice.
- Pradeep S. Rajendran
- , Rosemary C. Challis
- & Kalyanam Shivkumar
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| Open AccessC9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity
Repeat expansion mutation in C9ORF72 is the most common cause of familial ALS. Here, the authors generate motor neurons from cells of patients with C9ORF72 mutations, and characterize changes in gene expression in these motor neurons compared to genetically corrected lines, which suggest that glutamate receptor subunit GluA1 is dysregulated in this form of ALS.
- Bhuvaneish T. Selvaraj
- , Matthew R. Livesey
- & Siddharthan Chandran
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| Open AccessHDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients
Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor neurons. Using motor neurons derived from induced pluripotent stem cells from patients with ALS and FUS mutations, the authors demonstrate that axonal transport deficits that are observed in these cells can be rescued by HDAC6 inhibition.
- Wenting Guo
- , Maximilian Naujock
- & Ludo Van Den Bosch
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miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3
microRNAs have emerged as important components of numerous gene regulatory networks. Here the authors demonstrate that miR-218 is an essential component of the gene regulatory network that controls motor neuron fate specification in the developing spinal cord.
- Karen P. Thiebes
- , Heejin Nam
- & Soo-Kyung Lee
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| Open AccessCell-selective labelling of proteomes in Drosophila melanogaster
Mutated tRNA synthetases can incorporate non-canonical amino acids into proteins. Erdmann et al. exploit this property to metabolically label newly synthesized proteins in selected cell types in Drosophila, and demonstrate their detection using proteomics (BONCAT) and fluorescence imaging (FUNCAT).
- Ines Erdmann
- , Kathrin Marter
- & Daniela C. Dieterich
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| Open AccessFoxp1-mediated programming of limb-innervating motor neurons from mouse and human embryonic stem cells
The differentiation of spinal motor neurons (MNs) from mouse and human embryonic stem cells provides opportunities to model MN development and disease, but most protocols produce only a subset of the MN subtypes found in vivo. Here the authors show that limb projecting lateral motor column MNs can be efficiently generated though the expression of Foxp1.
- Katrina L. Adams
- , David L. Rousso
- & Bennett G. Novitch
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| Open AccessProspective errors determine motor learning
Motor learning is characterized by diverse cognitive processes, which lack a unified theoretical framework. Here, Takiyama et al.present a model demonstrating that motor learning is determined by prospective errors, which they test in a specially designed visuomotor adaptation task.
- Ken Takiyama
- , Masaya Hirashima
- & Daichi Nozaki
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| Open AccessHuman iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects spinal cord motor neurons. Here the authors use induced pluripotent stem cell-derived motor neurons obtained from patients with ALS-linked mutations, and find functional deficits resulting from a progressive decrease in voltage-activated Na+ and K+currents that occur in the absence of cell death.
- Anna-Claire Devlin
- , Karen Burr
- & Gareth B. Miles
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Article
| Open AccessVAV-1 acts in a single interneuron to inhibit motor circuit activity in Caenorhabditis elegans
VAV proteins are guanine nucleotide exchange factors that have various neuromodulatory roles in the nervous system. Here, Fry et al. show that in Caenorhabditis elegans, VAV-1 negatively regulates locomotor speed and only needs to be expressed in a specific interneuron to do so.
- Amanda L. Fry
- , Jocelyn T. Laboy
- & Kenneth R. Norman
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High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1
Motor neurons generated from human pluripotent stem cells are used for disease modelling and drug screening. Here the authors present a protocol for efficient generation of mature spinal motor neurons from human pluripotent stem cells by precisely timing the application of the neural patterning molecule retinoic acid.
- Qiuhao Qu
- , Dong Li
- & Fei Wang
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Homeostatic regulation of dendritic dynamics in a motor map in vivo
Various homeostatic mechanisms have been implicated in regulating neuronal excitability. Kishore and Fetcho study homeostatic mechanisms in zebrafish and find they regulate topographic patterns of dendritic dynamics within pools of motoneurons, that map onto ordered patterns of recruitment during behaviour.
- Sandeep Kishore
- & Joseph R. Fetcho
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Vocalization frequency and duration are coded in separate hindbrain nuclei
Vocal communication is relatively common among fish: the midshipman being an example with a particularly wide dynamic range. In this paper, the authors demonstrate that different populations of hindbrain neurons are responsible for the frequency and duration of these calls.
- Boris P. Chagnaud
- , Robert Baker
- & Andrew H. Bass
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| Open AccessRetinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
There is much interest in generating motor neurons from embryonic stem cells because they may be useful for the study of neurodegenerative disease. Pataniet al. show that in the absence of retinoic acid, neurons with features of medial motor columnar neurons can be generated from human embryonic stem cells.
- R. Patani
- , A. J. Hollins
- & S. Chandran
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| Open AccessAncestry of motor innervation to pectoral fin and forelimb
It was previously thought that the nerves in the pectoral fin of fish came solely from the spinal cord. Here, motoneurons in ray-finned fish are shown to also originate from the hindbrain, demonstrating that innervation was from both the hindbrain and the spinal cord in ancesteral vertebrates.
- Leung-Hang Ma
- , Edwin Gilland
- & Robert Baker