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  • 1
    Publication Date: 2012-06-23
    Description: It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kinoshita, Masaharu -- Matsui, Ryosuke -- Kato, Shigeki -- Hasegawa, Taku -- Kasahara, Hironori -- Isa, Kaoru -- Watakabe, Akiya -- Yamamori, Tetsuo -- Nishimura, Yukio -- Alstermark, Bror -- Watanabe, Dai -- Kobayashi, Kazuto -- Isa, Tadashi -- England -- Nature. 2012 Jul 12;487(7406):235-8. doi: 10.1038/nature11206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722837" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dependovirus/genetics ; Green Fluorescent Proteins/metabolism ; Hand/*physiology ; Macaca ; Metalloendopeptidases/metabolism ; Motor Cortex/physiology ; Motor Neurons/*physiology ; *Neurosciences ; Synaptic Transmission/genetics/physiology ; Tetanus Toxin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-02-04
    Description: The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230338/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230338/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Azim, Eiman -- Jiang, Juan -- Alstermark, Bror -- Jessell, Thomas M -- NS033245/NS/NINDS NIH HHS/ -- R01 NS033245/NS/NINDS NIH HHS/ -- R01 NS080932/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Apr 17;508(7496):357-63. doi: 10.1038/nature13021. Epub 2014 Feb 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Kavli Institute for Brain Science, Mortimer B. Zuckerman Mind Brain Behavior Institute, Departments of Neuroscience and Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA. ; Department of Integrative Medical Biology, Section of Physiology, Umea University, Umea, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24487617" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebellum/physiology ; Feedback, Physiological ; Female ; Forelimb/*innervation/*physiology ; Interneurons/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Motor Neurons/*physiology ; Motor Skills/*physiology ; Movement/*physiology ; *Neural Pathways ; Optogenetics ; Psychomotor Performance/physiology ; Spinal Cord/*cytology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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