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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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Variance of LRN neuronal spiking and motor neuron EPSPs during PN terminal photo-stimulation, and evaluation of electrically-induced antidromic action potentials in PNsa, LRN neurons exhibited low jitter spiking (mean variance 0.009 +/− 0.006 ms2 s.d.; n = 9), consistent with monosynaptic input, during photo-stimulation of PN terminals in the LRN. This contrasts sharply with large motor neuron (MN) EPSP jitter during PN terminal photo-stimulation (mean variance 0.28 +/− 0.35 ms2 s.d.; n = 11), consistent with recruitment of a polysynaptic pathway. An ~30-fold increase in the variance for MN EPSPs as compared to LRN spiking can be seen. Variance was calculated with respect to the shortest latency response. b, Antidromic spiking of PN somata evoked by electrical stimulation of their ascending (LRN; light blue) and descending (C7; dark blue) axonal branches occurred with a mean latency of ~1 ms in each case, adding to a total conduction time of about 2 ms (black). Subtracting approximate axonal activation and two soma invasion times, which are likely each on the order of 0.4 ms19, provides an estimate for the conduction time of an antidromic action potential across both branches of the PN – in the ~1 – 1.2 ms range. See Supplementary Discussion.
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Figure 13: Variance of LRN neuronal spiking and motor neuron EPSPs during PN terminal photo-stimulation, and evaluation of electrically-induced antidromic action potentials in PNsa, LRN neurons exhibited low jitter spiking (mean variance 0.009 +/− 0.006 ms2 s.d.; n = 9), consistent with monosynaptic input, during photo-stimulation of PN terminals in the LRN. This contrasts sharply with large motor neuron (MN) EPSP jitter during PN terminal photo-stimulation (mean variance 0.28 +/− 0.35 ms2 s.d.; n = 11), consistent with recruitment of a polysynaptic pathway. An ~30-fold increase in the variance for MN EPSPs as compared to LRN spiking can be seen. Variance was calculated with respect to the shortest latency response. b, Antidromic spiking of PN somata evoked by electrical stimulation of their ascending (LRN; light blue) and descending (C7; dark blue) axonal branches occurred with a mean latency of ~1 ms in each case, adding to a total conduction time of about 2 ms (black). Subtracting approximate axonal activation and two soma invasion times, which are likely each on the order of 0.4 ms19, provides an estimate for the conduction time of an antidromic action potential across both branches of the PN – in the ~1 – 1.2 ms range. See Supplementary Discussion.

Mentions: A core feature of internal copy models is a rapid modulation of motor output10-14. We therefore explored how motor neurons are influenced by photo-stimulation of the internally-directed PN branch. Intracellular recording from forelimb-innervating motor neurons in anesthetized Chx10-Cre mice injected at C3-T1 with AAV-FLEX-hChR2-YFP revealed polysynaptic EPSPs after LRN photo-stimulation (Fig. 6e; upper black traces; mean onset latency 4.18 +/− 0.75 ms s.d.; mean variance 0.28 +/− 0.35 ms2 s.d.). In contrast, recruitment of the pre-motor branch by photo-stimulation of PN cell bodies revealed monosynaptic motor neuron EPSPs (Fig. 6e; lower black traces; mean onset latency 2.60 +/− 0.20 ms s.d.; mean variance 0.014 +/− 0.009 ms2 s.d.). Recording from LRN neurons during PN terminal photo-stimulation revealed short-latency, monosynaptic activation (mean onset latency 0.87 +/− 0.10 ms s.d. from local depolarization; mean variance 0.009 +/− 0.006 ms2 s.d.), evidence that the variability in motor neuron EPSP onset after PN terminal photo-stimulation arises downstream of the PN-LRN synapse (Extended Data Fig. 7a). These findings reinforce the view that photo-stimulation of PN terminals activates motor neurons through a polysynaptic pathway and not by antidromic recruitment of the pre-motor branch (Supplementary Discussion, Extended Data Fig. 7b).


Skilled reaching relies on a V2a propriospinal internal copy circuit.

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

Variance of LRN neuronal spiking and motor neuron EPSPs during PN terminal photo-stimulation, and evaluation of electrically-induced antidromic action potentials in PNsa, LRN neurons exhibited low jitter spiking (mean variance 0.009 +/− 0.006 ms2 s.d.; n = 9), consistent with monosynaptic input, during photo-stimulation of PN terminals in the LRN. This contrasts sharply with large motor neuron (MN) EPSP jitter during PN terminal photo-stimulation (mean variance 0.28 +/− 0.35 ms2 s.d.; n = 11), consistent with recruitment of a polysynaptic pathway. An ~30-fold increase in the variance for MN EPSPs as compared to LRN spiking can be seen. Variance was calculated with respect to the shortest latency response. b, Antidromic spiking of PN somata evoked by electrical stimulation of their ascending (LRN; light blue) and descending (C7; dark blue) axonal branches occurred with a mean latency of ~1 ms in each case, adding to a total conduction time of about 2 ms (black). Subtracting approximate axonal activation and two soma invasion times, which are likely each on the order of 0.4 ms19, provides an estimate for the conduction time of an antidromic action potential across both branches of the PN – in the ~1 – 1.2 ms range. See Supplementary Discussion.
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Figure 13: Variance of LRN neuronal spiking and motor neuron EPSPs during PN terminal photo-stimulation, and evaluation of electrically-induced antidromic action potentials in PNsa, LRN neurons exhibited low jitter spiking (mean variance 0.009 +/− 0.006 ms2 s.d.; n = 9), consistent with monosynaptic input, during photo-stimulation of PN terminals in the LRN. This contrasts sharply with large motor neuron (MN) EPSP jitter during PN terminal photo-stimulation (mean variance 0.28 +/− 0.35 ms2 s.d.; n = 11), consistent with recruitment of a polysynaptic pathway. An ~30-fold increase in the variance for MN EPSPs as compared to LRN spiking can be seen. Variance was calculated with respect to the shortest latency response. b, Antidromic spiking of PN somata evoked by electrical stimulation of their ascending (LRN; light blue) and descending (C7; dark blue) axonal branches occurred with a mean latency of ~1 ms in each case, adding to a total conduction time of about 2 ms (black). Subtracting approximate axonal activation and two soma invasion times, which are likely each on the order of 0.4 ms19, provides an estimate for the conduction time of an antidromic action potential across both branches of the PN – in the ~1 – 1.2 ms range. See Supplementary Discussion.
Mentions: A core feature of internal copy models is a rapid modulation of motor output10-14. We therefore explored how motor neurons are influenced by photo-stimulation of the internally-directed PN branch. Intracellular recording from forelimb-innervating motor neurons in anesthetized Chx10-Cre mice injected at C3-T1 with AAV-FLEX-hChR2-YFP revealed polysynaptic EPSPs after LRN photo-stimulation (Fig. 6e; upper black traces; mean onset latency 4.18 +/− 0.75 ms s.d.; mean variance 0.28 +/− 0.35 ms2 s.d.). In contrast, recruitment of the pre-motor branch by photo-stimulation of PN cell bodies revealed monosynaptic motor neuron EPSPs (Fig. 6e; lower black traces; mean onset latency 2.60 +/− 0.20 ms s.d.; mean variance 0.014 +/− 0.009 ms2 s.d.). Recording from LRN neurons during PN terminal photo-stimulation revealed short-latency, monosynaptic activation (mean onset latency 0.87 +/− 0.10 ms s.d. from local depolarization; mean variance 0.009 +/− 0.006 ms2 s.d.), evidence that the variability in motor neuron EPSP onset after PN terminal photo-stimulation arises downstream of the PN-LRN synapse (Extended Data Fig. 7a). These findings reinforce the view that photo-stimulation of PN terminals activates motor neurons through a polysynaptic pathway and not by antidromic recruitment of the pre-motor branch (Supplementary Discussion, Extended Data Fig. 7b).

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