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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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Excitatory PNs are a V2a IN subpopulationa, Unilateral C3/C4 injection of AAV-FLEX-hChR2-YFP into Chx10::tdT mice. b, 82% (+/− 7% s.e.m.; n = 2) of C3/C4 tdT+ V2a INs were transduced (C4, yellow neurons, arrows; C8, red only neurons, arrowheads). c, YFP+ V2a INs project to LRN. Neurons, labeled with NeuroTrace (blue), studded with vGluT2+ (red), YFP+ boutons (arrows, yellow boutons). Sparse YFP+ axonal labeling also in facial nucleus. d, C7/C8 ChAT+ MNs (blue) contacted by vGluT2+ (red), YFP+ boutons (arrows, yellow boutons).
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Figure 2: Excitatory PNs are a V2a IN subpopulationa, Unilateral C3/C4 injection of AAV-FLEX-hChR2-YFP into Chx10::tdT mice. b, 82% (+/− 7% s.e.m.; n = 2) of C3/C4 tdT+ V2a INs were transduced (C4, yellow neurons, arrows; C8, red only neurons, arrowheads). c, YFP+ V2a INs project to LRN. Neurons, labeled with NeuroTrace (blue), studded with vGluT2+ (red), YFP+ boutons (arrows, yellow boutons). Sparse YFP+ axonal labeling also in facial nucleus. d, C7/C8 ChAT+ MNs (blue) contacted by vGluT2+ (red), YFP+ boutons (arrows, yellow boutons).

Mentions: V2a INs represent a major class of ipsilateral, excitatory pre-motor interneurons in the ventral spinal cord, and express the homeodomain transcription factor Chx10 (Fig. 2a)27,28. To assess whether excitatory PNs are included within the V2a cohort we crossed Chx10-Cre mice with a Rosa-lsl-tdTomato (-tdT) reporter line, generating Chx10::tdT mice. V2a INs were labeled by unilateral injection of a Cre-dependent adeno-associated viral vector expressing a Channelrhodopsin2-YFP fusion (AAV-FLEX-hChR2-YFP) into rostral cervical segments of adult Chx10::tdT mice (Fig. 2a).


Skilled reaching relies on a V2a propriospinal internal copy circuit.

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

Excitatory PNs are a V2a IN subpopulationa, Unilateral C3/C4 injection of AAV-FLEX-hChR2-YFP into Chx10::tdT mice. b, 82% (+/− 7% s.e.m.; n = 2) of C3/C4 tdT+ V2a INs were transduced (C4, yellow neurons, arrows; C8, red only neurons, arrowheads). c, YFP+ V2a INs project to LRN. Neurons, labeled with NeuroTrace (blue), studded with vGluT2+ (red), YFP+ boutons (arrows, yellow boutons). Sparse YFP+ axonal labeling also in facial nucleus. d, C7/C8 ChAT+ MNs (blue) contacted by vGluT2+ (red), YFP+ boutons (arrows, yellow boutons).
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Related In: Results  -  Collection

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Figure 2: Excitatory PNs are a V2a IN subpopulationa, Unilateral C3/C4 injection of AAV-FLEX-hChR2-YFP into Chx10::tdT mice. b, 82% (+/− 7% s.e.m.; n = 2) of C3/C4 tdT+ V2a INs were transduced (C4, yellow neurons, arrows; C8, red only neurons, arrowheads). c, YFP+ V2a INs project to LRN. Neurons, labeled with NeuroTrace (blue), studded with vGluT2+ (red), YFP+ boutons (arrows, yellow boutons). Sparse YFP+ axonal labeling also in facial nucleus. d, C7/C8 ChAT+ MNs (blue) contacted by vGluT2+ (red), YFP+ boutons (arrows, yellow boutons).
Mentions: V2a INs represent a major class of ipsilateral, excitatory pre-motor interneurons in the ventral spinal cord, and express the homeodomain transcription factor Chx10 (Fig. 2a)27,28. To assess whether excitatory PNs are included within the V2a cohort we crossed Chx10-Cre mice with a Rosa-lsl-tdTomato (-tdT) reporter line, generating Chx10::tdT mice. V2a INs were labeled by unilateral injection of a Cre-dependent adeno-associated viral vector expressing a Channelrhodopsin2-YFP fusion (AAV-FLEX-hChR2-YFP) into rostral cervical segments of adult Chx10::tdT mice (Fig. 2a).

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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