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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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LRN-projecting V2a INs are restricted to cervical segmentsa,AAV-FLEX-hChR2-YFP was injected unilaterally into C6-T1, mid thoracic and mid lumbar spinal cord of adult Chx10-Cre mice. YFP+ projections to the LRN could be identified following C3-C4 (see Fig. 2) and C6-T1 V2a IN transduction, but were minimal or absent following thoracic or lumbar transduction. b, Dual injection of CTB into the LRN (red) and WGA into triceps brachii muscle (blue) labeled YFP+ V2a INs (green) in intermediate levels of cervical cord in Chx10-Cre;Rosa-lsl-YFP mice. CTB also labeled YFPoff neurons, potentially corresponding to inhibitory PNs46.
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Figure 7: LRN-projecting V2a INs are restricted to cervical segmentsa,AAV-FLEX-hChR2-YFP was injected unilaterally into C6-T1, mid thoracic and mid lumbar spinal cord of adult Chx10-Cre mice. YFP+ projections to the LRN could be identified following C3-C4 (see Fig. 2) and C6-T1 V2a IN transduction, but were minimal or absent following thoracic or lumbar transduction. b, Dual injection of CTB into the LRN (red) and WGA into triceps brachii muscle (blue) labeled YFP+ V2a INs (green) in intermediate levels of cervical cord in Chx10-Cre;Rosa-lsl-YFP mice. CTB also labeled YFPoff neurons, potentially corresponding to inhibitory PNs46.

Mentions: With this labeling strategy >80% of all rostral cervical tdT+ V2a INs selectively expressed YFP (Fig. 2b). The LRN contained a dense network of YFP+ axons, and individual LRN neurons were studded with vGluT2+, YFP+ V2a-derived boutons (Fig. 2c). Similarly, C7/C8 level ChAT+ motor neurons were contacted by vGluT2+, YFP+ V2a boutons (Fig. 2d). We detected a similar pattern of bouton labeling on LRN and motor neurons after viral injection at C6-T1 levels, but little YFP+ labeling in the LRN after viral injection at more caudal levels (Extended Data Fig. 1a, Supplementary Note 3)20. Thus V2a neurons within C3 to T1 segments provide glutamatergic input to LRN and motor neurons.


Skilled reaching relies on a V2a propriospinal internal copy circuit.

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

LRN-projecting V2a INs are restricted to cervical segmentsa,AAV-FLEX-hChR2-YFP was injected unilaterally into C6-T1, mid thoracic and mid lumbar spinal cord of adult Chx10-Cre mice. YFP+ projections to the LRN could be identified following C3-C4 (see Fig. 2) and C6-T1 V2a IN transduction, but were minimal or absent following thoracic or lumbar transduction. b, Dual injection of CTB into the LRN (red) and WGA into triceps brachii muscle (blue) labeled YFP+ V2a INs (green) in intermediate levels of cervical cord in Chx10-Cre;Rosa-lsl-YFP mice. CTB also labeled YFPoff neurons, potentially corresponding to inhibitory PNs46.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230338&req=5

Figure 7: LRN-projecting V2a INs are restricted to cervical segmentsa,AAV-FLEX-hChR2-YFP was injected unilaterally into C6-T1, mid thoracic and mid lumbar spinal cord of adult Chx10-Cre mice. YFP+ projections to the LRN could be identified following C3-C4 (see Fig. 2) and C6-T1 V2a IN transduction, but were minimal or absent following thoracic or lumbar transduction. b, Dual injection of CTB into the LRN (red) and WGA into triceps brachii muscle (blue) labeled YFP+ V2a INs (green) in intermediate levels of cervical cord in Chx10-Cre;Rosa-lsl-YFP mice. CTB also labeled YFPoff neurons, potentially corresponding to inhibitory PNs46.
Mentions: With this labeling strategy >80% of all rostral cervical tdT+ V2a INs selectively expressed YFP (Fig. 2b). The LRN contained a dense network of YFP+ axons, and individual LRN neurons were studded with vGluT2+, YFP+ V2a-derived boutons (Fig. 2c). Similarly, C7/C8 level ChAT+ motor neurons were contacted by vGluT2+, YFP+ V2a boutons (Fig. 2d). We detected a similar pattern of bouton labeling on LRN and motor neurons after viral injection at C6-T1 levels, but little YFP+ labeling in the LRN after viral injection at more caudal levels (Extended Data Fig. 1a, Supplementary Note 3)20. Thus V2a neurons within C3 to T1 segments provide glutamatergic input to LRN and motor neurons.

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