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Skilled reaching relies on a V2a propriospinal internal copy circuit.

Azim E, Jiang J, Alstermark B, Jessell TM - Nature (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Identification of mouse PNsa, PNs receive direct and indirect supraspinal (corticospinal–CS; reticulospinal–RS) and sensory (S) input. PNs innervate cervical motor neurons (MN) and LRN neurons that project to cerebellum (CB). b,In vivo extracellular recordings (C3/C4) while stimulating LRN (20-100 μA) and C7 ventral horn (40 μA) revealed antidromic spikes (arrows) and collision (red arrowheads; n = 12). c, Intracellular MN recordings during LRN stimulation revealed monosynaptic EPSPs (100 μA; n = 29). LRN-induced EPSPs summate with monosynaptic EPSPs elicited by RS stimulation (100 μA; n = 34; arrowheads, EPSP onset). d, Extracellular PN recordings, identified via C7 (17 μA; blue arrows) and LRN stimulation (not shown), revealed monosynaptic spikes following RS stimulation (3 × 50 μA; red arrows; n = 14) and collision (red arrowheads; n = 17). See Supplementary Note 1.
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Figure 1: Identification of mouse PNsa, PNs receive direct and indirect supraspinal (corticospinal–CS; reticulospinal–RS) and sensory (S) input. PNs innervate cervical motor neurons (MN) and LRN neurons that project to cerebellum (CB). b,In vivo extracellular recordings (C3/C4) while stimulating LRN (20-100 μA) and C7 ventral horn (40 μA) revealed antidromic spikes (arrows) and collision (red arrowheads; n = 12). c, Intracellular MN recordings during LRN stimulation revealed monosynaptic EPSPs (100 μA; n = 29). LRN-induced EPSPs summate with monosynaptic EPSPs elicited by RS stimulation (100 μA; n = 34; arrowheads, EPSP onset). d, Extracellular PN recordings, identified via C7 (17 μA; blue arrows) and LRN stimulation (not shown), revealed monosynaptic spikes following RS stimulation (3 × 50 μA; red arrows; n = 14) and collision (red arrowheads; n = 17). See Supplementary Note 1.

Mentions: One class of spinal interneuron, cervical propriospinal neurons (here referred to as PNs), has long been implicated in the control of forelimb behavior15,16. In cat and primate, PNs comprise excitatory and inhibitory neuronal subtypes that serve as intermediary relays for descending motor commands16,17. PNs are characterized by an ipsilateral bifurcated output: one axonal branch projects caudally to the cervical motor neurons that control forelimb muscles18,19, and the other projects rostrally to the lateral reticular nucleus (LRN)20, a pre-cerebellar relay21-24(Fig. 1a). In principle, the intriguing duality of PN axonal projections offers a simple anatomical substrate for the internal copying of pre-motor signals. In cat, severing the pre-motor axonal branch of PNs by lesioning the ventrolateral funiculus perturbs reaching but not grasping25, whereas silencing PN output in monkey perturbs both reaching and grasping26. Neither of these manipulations, however, has addressed the relevance of an internal copy branch for on-line refinement of motor output.


Skilled reaching relies on a V2a propriospinal internal copy circuit.

Azim E, Jiang J, Alstermark B, Jessell TM - Nature (2014)

Identification of mouse PNsa, PNs receive direct and indirect supraspinal (corticospinal–CS; reticulospinal–RS) and sensory (S) input. PNs innervate cervical motor neurons (MN) and LRN neurons that project to cerebellum (CB). b,In vivo extracellular recordings (C3/C4) while stimulating LRN (20-100 μA) and C7 ventral horn (40 μA) revealed antidromic spikes (arrows) and collision (red arrowheads; n = 12). c, Intracellular MN recordings during LRN stimulation revealed monosynaptic EPSPs (100 μA; n = 29). LRN-induced EPSPs summate with monosynaptic EPSPs elicited by RS stimulation (100 μA; n = 34; arrowheads, EPSP onset). d, Extracellular PN recordings, identified via C7 (17 μA; blue arrows) and LRN stimulation (not shown), revealed monosynaptic spikes following RS stimulation (3 × 50 μA; red arrows; n = 14) and collision (red arrowheads; n = 17). See Supplementary Note 1.
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Figure 1: Identification of mouse PNsa, PNs receive direct and indirect supraspinal (corticospinal–CS; reticulospinal–RS) and sensory (S) input. PNs innervate cervical motor neurons (MN) and LRN neurons that project to cerebellum (CB). b,In vivo extracellular recordings (C3/C4) while stimulating LRN (20-100 μA) and C7 ventral horn (40 μA) revealed antidromic spikes (arrows) and collision (red arrowheads; n = 12). c, Intracellular MN recordings during LRN stimulation revealed monosynaptic EPSPs (100 μA; n = 29). LRN-induced EPSPs summate with monosynaptic EPSPs elicited by RS stimulation (100 μA; n = 34; arrowheads, EPSP onset). d, Extracellular PN recordings, identified via C7 (17 μA; blue arrows) and LRN stimulation (not shown), revealed monosynaptic spikes following RS stimulation (3 × 50 μA; red arrows; n = 14) and collision (red arrowheads; n = 17). See Supplementary Note 1.
Mentions: One class of spinal interneuron, cervical propriospinal neurons (here referred to as PNs), has long been implicated in the control of forelimb behavior15,16. In cat and primate, PNs comprise excitatory and inhibitory neuronal subtypes that serve as intermediary relays for descending motor commands16,17. PNs are characterized by an ipsilateral bifurcated output: one axonal branch projects caudally to the cervical motor neurons that control forelimb muscles18,19, and the other projects rostrally to the lateral reticular nucleus (LRN)20, a pre-cerebellar relay21-24(Fig. 1a). In principle, the intriguing duality of PN axonal projections offers a simple anatomical substrate for the internal copying of pre-motor signals. In cat, severing the pre-motor axonal branch of PNs by lesioning the ventrolateral funiculus perturbs reaching but not grasping25, whereas silencing PN output in monkey perturbs both reaching and grasping26. Neither of these manipulations, however, has addressed the relevance of an internal copy branch for on-line refinement of motor output.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus