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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-stimulation of PN input to the LRN before and after cerebellar lesiona, Post-physiology histology confirmed intact inferior cerebellar peduncles (ICP) in control mice and bilateral lesion of ICP (red arrowheads; n = 4) and complete removal of cerebellar cortex and deep cerebellar nuclei (n = 1) in experimental mice. b, Cerebellar lesions resulted in no change in LRN field potential size during PN terminal photo-stimulation (n = 2; two-tailed paired t-test). c, In non-lesioned mice, C7 field potential recordings revealed that photo-stimulation of PN terminals in the LRN (black traces) or PN somata in C4 (gray traces) elicited responses restricted to ventral regions of the gray matter, near motor neurons and their dendrites. Field onsets (arrowheads) were consistently longer following LRN vs. C4 photo-stimulation (also see Fig. 6e). Schematic depicts axial section of C7 and recording electrode depths. Roman numerals indicate Rexed laminae.
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Figure 14: Photo-stimulation of PN input to the LRN before and after cerebellar lesiona, Post-physiology histology confirmed intact inferior cerebellar peduncles (ICP) in control mice and bilateral lesion of ICP (red arrowheads; n = 4) and complete removal of cerebellar cortex and deep cerebellar nuclei (n = 1) in experimental mice. b, Cerebellar lesions resulted in no change in LRN field potential size during PN terminal photo-stimulation (n = 2; two-tailed paired t-test). c, In non-lesioned mice, C7 field potential recordings revealed that photo-stimulation of PN terminals in the LRN (black traces) or PN somata in C4 (gray traces) elicited responses restricted to ventral regions of the gray matter, near motor neurons and their dendrites. Field onsets (arrowheads) were consistently longer following LRN vs. C4 photo-stimulation (also see Fig. 6e). Schematic depicts axial section of C7 and recording electrode depths. Roman numerals indicate Rexed laminae.

Mentions: To examine whether the PN-LRN internal copy pathway engages cerebellar circuits we severed LRN output to cerebellar cortex and deep cerebellar nuclei through bilateral transection of the inferior cerebellar peduncles, or by cerebellar extirpation (Extended Data Fig. 8a). These lesions did not impair synaptic activation of LRN neurons induced by PN terminal photo-stimulation (Extended Data Fig. 8b). Motor neuron responses were assessed by recording field potentials in C6/C7 ventral horn – revealing an onset latency and duration similar to that of motor neuron EPSPs (Fig. 6e; gray traces, Extended Data Fig. 8c, Supplementary Note 7). After cerebellar lesions, field potentials elicited by PN terminal photo-stimulation were reduced by up to ~65% (Fig. 6f), suggesting that both cerebellar and non-cerebellar output pathways37-39 mediate the PN-LRN control of motor output. Nevertheless, field potential onsets after lesions occurred with an additional delay of ~1 to 3 ms when compared with non-lesioned mice (Fig. 6f). Thus the cerebellar-directed PN internal copy pathway appears to be involved in rapid feedback modulation of motor output.


Skilled reaching relies on a V2a propriospinal internal copy circuit.

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

Photo-stimulation of PN input to the LRN before and after cerebellar lesiona, Post-physiology histology confirmed intact inferior cerebellar peduncles (ICP) in control mice and bilateral lesion of ICP (red arrowheads; n = 4) and complete removal of cerebellar cortex and deep cerebellar nuclei (n = 1) in experimental mice. b, Cerebellar lesions resulted in no change in LRN field potential size during PN terminal photo-stimulation (n = 2; two-tailed paired t-test). c, In non-lesioned mice, C7 field potential recordings revealed that photo-stimulation of PN terminals in the LRN (black traces) or PN somata in C4 (gray traces) elicited responses restricted to ventral regions of the gray matter, near motor neurons and their dendrites. Field onsets (arrowheads) were consistently longer following LRN vs. C4 photo-stimulation (also see Fig. 6e). Schematic depicts axial section of C7 and recording electrode depths. Roman numerals indicate Rexed laminae.
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Related In: Results  -  Collection

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Figure 14: Photo-stimulation of PN input to the LRN before and after cerebellar lesiona, Post-physiology histology confirmed intact inferior cerebellar peduncles (ICP) in control mice and bilateral lesion of ICP (red arrowheads; n = 4) and complete removal of cerebellar cortex and deep cerebellar nuclei (n = 1) in experimental mice. b, Cerebellar lesions resulted in no change in LRN field potential size during PN terminal photo-stimulation (n = 2; two-tailed paired t-test). c, In non-lesioned mice, C7 field potential recordings revealed that photo-stimulation of PN terminals in the LRN (black traces) or PN somata in C4 (gray traces) elicited responses restricted to ventral regions of the gray matter, near motor neurons and their dendrites. Field onsets (arrowheads) were consistently longer following LRN vs. C4 photo-stimulation (also see Fig. 6e). Schematic depicts axial section of C7 and recording electrode depths. Roman numerals indicate Rexed laminae.
Mentions: To examine whether the PN-LRN internal copy pathway engages cerebellar circuits we severed LRN output to cerebellar cortex and deep cerebellar nuclei through bilateral transection of the inferior cerebellar peduncles, or by cerebellar extirpation (Extended Data Fig. 8a). These lesions did not impair synaptic activation of LRN neurons induced by PN terminal photo-stimulation (Extended Data Fig. 8b). Motor neuron responses were assessed by recording field potentials in C6/C7 ventral horn – revealing an onset latency and duration similar to that of motor neuron EPSPs (Fig. 6e; gray traces, Extended Data Fig. 8c, Supplementary Note 7). After cerebellar lesions, field potentials elicited by PN terminal photo-stimulation were reduced by up to ~65% (Fig. 6f), suggesting that both cerebellar and non-cerebellar output pathways37-39 mediate the PN-LRN control of motor output. Nevertheless, field potential onsets after lesions occurred with an additional delay of ~1 to 3 ms when compared with non-lesioned mice (Fig. 6f). Thus the cerebellar-directed PN internal copy pathway appears to be involved in rapid feedback modulation 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