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Even-Skipped(+) Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude.

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Heckscher, Ellie S 
Zarin, Aref Arzan 
Faumont, Serge 
Clark, Matthew Q 
Manning, Laurina 


Bilaterally symmetric motor patterns--those in which left-right pairs of muscles contract synchronously and with equal amplitude (such as breathing, smiling, whisking, and locomotion)--are widespread throughout the animal kingdom. Yet, surprisingly little is known about the underlying neural circuits. We performed a thermogenetic screen to identify neurons required for bilaterally symmetric locomotion in Drosophila larvae and identified the evolutionarily conserved Even-skipped(+) interneurons (Eve/Evx). Activation or ablation of Eve(+) interneurons disrupted bilaterally symmetric muscle contraction amplitude, without affecting the timing of motor output. Eve(+) interneurons are not rhythmically active and thus function independently of the locomotor CPG. GCaMP6 calcium imaging of Eve(+) interneurons in freely moving larvae showed left-right asymmetric activation that correlated with larval behavior. TEM reconstruction of Eve(+) interneuron inputs and outputs showed that the Eve(+) interneurons are at the core of a sensorimotor circuit capable of detecting and modifying body wall muscle contraction.



Animals, Animals, Genetically Modified, Drosophila Proteins, Functional Laterality, Homeodomain Proteins, Interneurons, Muscle Contraction, Nerve Net, Psychomotor Performance, Transcription Factors

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Elsevier BV
Wellcome Trust (092986/Z/10/Z)
This work was supported by NIH grant MH051383 (S.R.L.), American Heart Association #0920025G post-doctoral fellowship (E.S.H.), and the Howard Hughes Medical Institute, where C.Q.D. is an Investigator. M.L. was supported by a grant from the Wellcome Trust (092986/Z) and by an Isaac Newton Trust/Wellcome Trust ISSF Research Grant. We thank the HHMI Janelia Fly EM Project Team for providing the raw data of the whole CNS EM volume.