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dc.contributor.authorAllodi, Ilary
dc.contributor.authorMontañana-Rosell, Roser
dc.contributor.authorSelvan, Raghavendra
dc.contributor.authorLöw, Peter
dc.contributor.authorKiehn, Ole
dc.date.accessioned2023-01-30T10:30:19Z
dc.date.available2023-01-30T10:30:19Z
dc.date.issued2021-05-31
dc.identifier283153646
dc.identifier814192fe-4041-4338-b4d7-7b6721e646f3
dc.identifier34059686
dc.identifier85107319867
dc.identifier.citationAllodi , I , Montañana-Rosell , R , Selvan , R , Löw , P & Kiehn , O 2021 , ' Locomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neurons ' , Nature Communications , vol. 12 , 3251 . https://doi.org/10.1038/s41467-021-23224-7en
dc.identifier.issn2041-1723
dc.identifier.otherPubMedCentral: PMC8166981
dc.identifier.otherORCID: /0000-0003-4361-163X/work/128097828
dc.identifier.urihttps://hdl.handle.net/10023/26846
dc.descriptionFunding: This work was supported by the Lundbeck Foundation (I.A.), the Björklund foundation (I.A.), the A.P. Møller foundation (I.A.), the Novo Nordisk Laureate Program (O.K., NNF15OC0014186), The Lundbeck Foundation (O.K.), the Louis-Hansen foundation (R.M.R.) and The Faculty of Health and Medical Sciences (O.K.).en
dc.description.abstractALS is characterized by progressive inability to execute movements. Motor neurons innervating fast-twitch muscle-fibers preferentially degenerate. The reason for this differential vulnerability and its consequences on motor output is not known. Here, we uncover that fast motor neurons receive stronger inhibitory synaptic inputs than slow motor neurons, and disease progression in the SOD1G93A mouse model leads to specific loss of inhibitory synapses onto fast motor neurons. Inhibitory V1 interneurons show similar innervation pattern and loss of synapses. Moreover, from postnatal day 63, there is a loss of V1 interneurons in the SOD1G93A mouse. The V1 interneuron degeneration appears before motor neuron death and is paralleled by the development of a specific locomotor deficit affecting speed and limb coordination. This distinct ALS-induced locomotor deficit is phenocopied in wild-type mice but not in SOD1G93A mice after appearing of the locomotor phenotype when V1 spinal interneurons are silenced. Our study identifies a potential source of non-autonomous motor neuronal vulnerability in ALS and links ALS-induced changes in locomotor phenotype to inhibitory V1-interneurons.
dc.format.extent18
dc.format.extent9205103
dc.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.subjectAmyotrophic Lateral Sclerosis (ALS)/geneticsen
dc.subjectAnimalsen
dc.subjectDisease Models, Animalen
dc.subjectFemaleen
dc.subjectHomeodomain Proteins/metabolismen
dc.subjectHumansen
dc.subjectInterneurons/pathologyen
dc.subjectLocomotion/physiologyen
dc.subjectMaleen
dc.subjectMiceen
dc.subjectMice, Transgenicen
dc.subjectMotor Neurons/pathologyen
dc.subjectMuscle Fibers, Fast-Twitch/physiologyen
dc.subjectNeuromuscular Junction/pathologyen
dc.subjectSpinal Cord/cytologyen
dc.subjectSuperoxide Dismutase/geneticsen
dc.subjectSuperoxide Dismutase-1/geneticsen
dc.subjectRC0321 Neuroscience. Biological psychiatry. Neuropsychiatryen
dc.subjectQH426 Geneticsen
dc.subjectDASen
dc.subjectMCCen
dc.subject.lccRC0321en
dc.subject.lccQH426en
dc.titleLocomotor deficits in a mouse model of ALS are paralleled by loss of V1-interneuron connections onto fast motor neuronsen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.identifier.doi10.1038/s41467-021-23224-7
dc.description.statusPeer revieweden


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