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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 LRN does not elicit antidromic spikesa, PNs in C6 were identified antidromically by electrical stimulation from the LRN (40 μA; arrows) and C7 ventral horn (40 μA; not shown) and by spike collision (not shown). b, Cervical photo-stimulation of the same PN cell bodies activated 69.2% of PNs (n = 9/13; green arrows indicate single spikes), as identified by collision of the LRN antidromic spike (lower red traces; red arrowheads; compare with antidromic spike in a; two lower black traces exhibit failed collision). c, In the same PNs, photo-stimulation of PN terminals in the LRN did not trigger antidromic spikes that invaded the cell body (0/31 PNs; 0/3 in control mice), whereas electrical stimulation in the LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in a). Also see Fig. 5b-d.
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Figure 11: Photo-activation of PN terminals in the LRN does not elicit antidromic spikesa, PNs in C6 were identified antidromically by electrical stimulation from the LRN (40 μA; arrows) and C7 ventral horn (40 μA; not shown) and by spike collision (not shown). b, Cervical photo-stimulation of the same PN cell bodies activated 69.2% of PNs (n = 9/13; green arrows indicate single spikes), as identified by collision of the LRN antidromic spike (lower red traces; red arrowheads; compare with antidromic spike in a; two lower black traces exhibit failed collision). c, In the same PNs, photo-stimulation of PN terminals in the LRN did not trigger antidromic spikes that invaded the cell body (0/31 PNs; 0/3 in control mice), whereas electrical stimulation in the LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in a). Also see Fig. 5b-d.

Mentions: We examined whether photo-stimulation of PN terminals in the LRN triggers antidromic action potentials. As above, PNs were identified by spike collision after electrical stimulation of LRN and C7 (Fig. 5b, Extended Data Fig. 5a). Photo-stimulation of identified PN cell bodies at cervical levels revealed that ~70% expressed ChR2, as determined by spike collision after LRN or C7 electrical stimulation (Fig. 5c, Extended Data Fig. 5b, Supplementary Note 6). For these PNs we compared the impact of local LRN electrical stimulation and focal LRN photo-stimulation, monitoring the incidence of antidromic spikes. Electrical stimulation of the LRN invariably elicited antidromic spikes in PNs, whereas LRN photo-stimulation never elicited spiking (0/31 PNs; Fig. 5d, Extended Data Fig. 5c). Thus photo-stimulation of ChR2+ PN terminals within the LRN activates the internally-directed pathway without eliciting antidromic action potentials (Supplementary Discussion).


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 LRN does not elicit antidromic spikesa, PNs in C6 were identified antidromically by electrical stimulation from the LRN (40 μA; arrows) and C7 ventral horn (40 μA; not shown) and by spike collision (not shown). b, Cervical photo-stimulation of the same PN cell bodies activated 69.2% of PNs (n = 9/13; green arrows indicate single spikes), as identified by collision of the LRN antidromic spike (lower red traces; red arrowheads; compare with antidromic spike in a; two lower black traces exhibit failed collision). c, In the same PNs, photo-stimulation of PN terminals in the LRN did not trigger antidromic spikes that invaded the cell body (0/31 PNs; 0/3 in control mice), whereas electrical stimulation in the LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in a). Also see Fig. 5b-d.
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Related In: Results  -  Collection

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Figure 11: Photo-activation of PN terminals in the LRN does not elicit antidromic spikesa, PNs in C6 were identified antidromically by electrical stimulation from the LRN (40 μA; arrows) and C7 ventral horn (40 μA; not shown) and by spike collision (not shown). b, Cervical photo-stimulation of the same PN cell bodies activated 69.2% of PNs (n = 9/13; green arrows indicate single spikes), as identified by collision of the LRN antidromic spike (lower red traces; red arrowheads; compare with antidromic spike in a; two lower black traces exhibit failed collision). c, In the same PNs, photo-stimulation of PN terminals in the LRN did not trigger antidromic spikes that invaded the cell body (0/31 PNs; 0/3 in control mice), whereas electrical stimulation in the LRN always produced antidromic spikes (lower traces; arrow; compare with antidromic spike in a). Also see Fig. 5b-d.
Mentions: We examined whether photo-stimulation of PN terminals in the LRN triggers antidromic action potentials. As above, PNs were identified by spike collision after electrical stimulation of LRN and C7 (Fig. 5b, Extended Data Fig. 5a). Photo-stimulation of identified PN cell bodies at cervical levels revealed that ~70% expressed ChR2, as determined by spike collision after LRN or C7 electrical stimulation (Fig. 5c, Extended Data Fig. 5b, Supplementary Note 6). For these PNs we compared the impact of local LRN electrical stimulation and focal LRN photo-stimulation, monitoring the incidence of antidromic spikes. Electrical stimulation of the LRN invariably elicited antidromic spikes in PNs, whereas LRN photo-stimulation never elicited spiking (0/31 PNs; Fig. 5d, Extended Data Fig. 5c). Thus photo-stimulation of ChR2+ PN terminals within the LRN activates the internally-directed pathway without eliciting antidromic action potentials (Supplementary Discussion).

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