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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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Photo-activation of PN terminals in the LRNa, Extracellular recording of LRN neurons antidromically activated from cerebellum (20 μA; purple arrows) during PN terminal photo-stimulation (473 nm) revealed repeated spiking (n = 8/21; blue arrows) and collision (red arrowheads, two collision failures in bottom traces). b, PNs in C3/C4 were identified by electrical stimulation from LRN (80 μA) and C7 (40 μA) and by collision (not shown). c, Photo-stimulation of the same PN cell bodies activated 69% of PNs (n = 9/13; green arrows), verified by collision of C7 spike (lower traces; red arrowheads; compare with antidromic spike in b). See Supplementary Note 6. d, In the same PNs, photo-stimulation of terminals in LRN did not trigger antidromic spikes (0/31 PNs; 0/3 control), whereas electrical stimulation in LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in b). See Extended Data Fig. 5.
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Figure 5: Photo-activation of PN terminals in the LRNa, Extracellular recording of LRN neurons antidromically activated from cerebellum (20 μA; purple arrows) during PN terminal photo-stimulation (473 nm) revealed repeated spiking (n = 8/21; blue arrows) and collision (red arrowheads, two collision failures in bottom traces). b, PNs in C3/C4 were identified by electrical stimulation from LRN (80 μA) and C7 (40 μA) and by collision (not shown). c, Photo-stimulation of the same PN cell bodies activated 69% of PNs (n = 9/13; green arrows), verified by collision of C7 spike (lower traces; red arrowheads; compare with antidromic spike in b). See Supplementary Note 6. d, In the same PNs, photo-stimulation of terminals in LRN did not trigger antidromic spikes (0/31 PNs; 0/3 control), whereas electrical stimulation in LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in b). See Extended Data Fig. 5.

Mentions: After viral injection we detected a dense network of ChR2-YFP+ fibers within the LRN (Fig. 2, Extended Data Fig. 1a). Extracellular recording from LRN neurons in anaesthetized mice revealed that focal photo-stimulation of PN terminals excited ~40% (n = 8/21) of neurons with cerebellar projections, assessed by spike collision after cerebellar stimulation, with no effect in virus-spared control mice (Fig. 5a, Extended Data Fig. 4a-c).


Skilled reaching relies on a V2a propriospinal internal copy circuit.

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

Photo-activation of PN terminals in the LRNa, Extracellular recording of LRN neurons antidromically activated from cerebellum (20 μA; purple arrows) during PN terminal photo-stimulation (473 nm) revealed repeated spiking (n = 8/21; blue arrows) and collision (red arrowheads, two collision failures in bottom traces). b, PNs in C3/C4 were identified by electrical stimulation from LRN (80 μA) and C7 (40 μA) and by collision (not shown). c, Photo-stimulation of the same PN cell bodies activated 69% of PNs (n = 9/13; green arrows), verified by collision of C7 spike (lower traces; red arrowheads; compare with antidromic spike in b). See Supplementary Note 6. d, In the same PNs, photo-stimulation of terminals in LRN did not trigger antidromic spikes (0/31 PNs; 0/3 control), whereas electrical stimulation in LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in b). See Extended Data Fig. 5.
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Figure 5: Photo-activation of PN terminals in the LRNa, Extracellular recording of LRN neurons antidromically activated from cerebellum (20 μA; purple arrows) during PN terminal photo-stimulation (473 nm) revealed repeated spiking (n = 8/21; blue arrows) and collision (red arrowheads, two collision failures in bottom traces). b, PNs in C3/C4 were identified by electrical stimulation from LRN (80 μA) and C7 (40 μA) and by collision (not shown). c, Photo-stimulation of the same PN cell bodies activated 69% of PNs (n = 9/13; green arrows), verified by collision of C7 spike (lower traces; red arrowheads; compare with antidromic spike in b). See Supplementary Note 6. d, In the same PNs, photo-stimulation of terminals in LRN did not trigger antidromic spikes (0/31 PNs; 0/3 control), whereas electrical stimulation in LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in b). See Extended Data Fig. 5.
Mentions: After viral injection we detected a dense network of ChR2-YFP+ fibers within the LRN (Fig. 2, Extended Data Fig. 1a). Extracellular recording from LRN neurons in anaesthetized mice revealed that focal photo-stimulation of PN terminals excited ~40% (n = 8/21) of neurons with cerebellar projections, assessed by spike collision after cerebellar stimulation, with no effect in virus-spared control mice (Fig. 5a, Extended Data Fig. 4a-c).

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