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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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Selective photo-activation of PN input to the LRNa, Population recordings in the LRN revealed photo-stimulation induced synaptic activation of LRN neurons across a range of optical fiber depths in and above the brainstem. Retraction of the optical fiber from the LRN (presumably resulting in a decrease in light exposure) resulted in a reduced amplitude of the LRN extracellular field potential (arrow), and, consequently in an increase in LRN neuronal firing latency. Schematic depicts coronal section of caudal brainstem and optical fiber depths. Sp5c, spinal trigeminal nucleus, caudal part; MLF, medial longitudinal fasciculus; IO, inferior olive; Pyr, pyramidal tract. b, Extracellular recording of LRN neurons antidromically activated from cerebellum (CB; 20 μA; purple arrows), with the optical fiber just dorsal to the LRN, revealed activation (blue arrows) and spike collision (red arrowheads) across a range of laser intensities (also see Fig. 5a). Increasing the light intensity caused more intense synaptic firing and a slight shortening of the latency from light onset. c, Extracellular recording of LRN neurons in control mice revealed no activation and no collision of the electrically-induced antidromic spike from the cerebellum (purple arrows) during photo-stimulation (n = 0/14 neurons).
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Figure 10: Selective photo-activation of PN input to the LRNa, Population recordings in the LRN revealed photo-stimulation induced synaptic activation of LRN neurons across a range of optical fiber depths in and above the brainstem. Retraction of the optical fiber from the LRN (presumably resulting in a decrease in light exposure) resulted in a reduced amplitude of the LRN extracellular field potential (arrow), and, consequently in an increase in LRN neuronal firing latency. Schematic depicts coronal section of caudal brainstem and optical fiber depths. Sp5c, spinal trigeminal nucleus, caudal part; MLF, medial longitudinal fasciculus; IO, inferior olive; Pyr, pyramidal tract. b, Extracellular recording of LRN neurons antidromically activated from cerebellum (CB; 20 μA; purple arrows), with the optical fiber just dorsal to the LRN, revealed activation (blue arrows) and spike collision (red arrowheads) across a range of laser intensities (also see Fig. 5a). Increasing the light intensity caused more intense synaptic firing and a slight shortening of the latency from light onset. c, Extracellular recording of LRN neurons in control mice revealed no activation and no collision of the electrically-induced antidromic spike from the cerebellum (purple arrows) during photo-stimulation (n = 0/14 neurons).

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)

Selective photo-activation of PN input to the LRNa, Population recordings in the LRN revealed photo-stimulation induced synaptic activation of LRN neurons across a range of optical fiber depths in and above the brainstem. Retraction of the optical fiber from the LRN (presumably resulting in a decrease in light exposure) resulted in a reduced amplitude of the LRN extracellular field potential (arrow), and, consequently in an increase in LRN neuronal firing latency. Schematic depicts coronal section of caudal brainstem and optical fiber depths. Sp5c, spinal trigeminal nucleus, caudal part; MLF, medial longitudinal fasciculus; IO, inferior olive; Pyr, pyramidal tract. b, Extracellular recording of LRN neurons antidromically activated from cerebellum (CB; 20 μA; purple arrows), with the optical fiber just dorsal to the LRN, revealed activation (blue arrows) and spike collision (red arrowheads) across a range of laser intensities (also see Fig. 5a). Increasing the light intensity caused more intense synaptic firing and a slight shortening of the latency from light onset. c, Extracellular recording of LRN neurons in control mice revealed no activation and no collision of the electrically-induced antidromic spike from the cerebellum (purple arrows) during photo-stimulation (n = 0/14 neurons).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230338&req=5

Figure 10: Selective photo-activation of PN input to the LRNa, Population recordings in the LRN revealed photo-stimulation induced synaptic activation of LRN neurons across a range of optical fiber depths in and above the brainstem. Retraction of the optical fiber from the LRN (presumably resulting in a decrease in light exposure) resulted in a reduced amplitude of the LRN extracellular field potential (arrow), and, consequently in an increase in LRN neuronal firing latency. Schematic depicts coronal section of caudal brainstem and optical fiber depths. Sp5c, spinal trigeminal nucleus, caudal part; MLF, medial longitudinal fasciculus; IO, inferior olive; Pyr, pyramidal tract. b, Extracellular recording of LRN neurons antidromically activated from cerebellum (CB; 20 μA; purple arrows), with the optical fiber just dorsal to the LRN, revealed activation (blue arrows) and spike collision (red arrowheads) across a range of laser intensities (also see Fig. 5a). Increasing the light intensity caused more intense synaptic firing and a slight shortening of the latency from light onset. c, Extracellular recording of LRN neurons in control mice revealed no activation and no collision of the electrically-induced antidromic spike from the cerebellum (purple arrows) during photo-stimulation (n = 0/14 neurons).
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