Musculotendon adaptations and preservation of spinal reflex pathways following agonist-to-antagonist tendon transfer

Lyle, Mark A.; Nichols, T. Richard; Kajtaz, Elma; Maas, Huub

doi:10.14814/phy2.13201

Cited by 5 publications

(5 citation statements)

References 60 publications

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“…The physiological significance of this Ia afferent circuit plasticity in the spinal cord ventral horn is not fully clear. Loss of Ia inputs manifests in joint discoordination and diminished performance after muscles are reinnervated, in particular for motor tasks requiring fast and accurate proprioceptive feedback (Cope et al, 1994;Abelew et al, 2000;Haftel et al, 2005;Maas et al, 2007;Bullinger et al, 2011;Sabatier et al, 2011;Lyle et al, 2017;Chang et al, 2018). On the other hand, deletion of Ia/II inputs might reduce connectivity incongruences between proprioceptors and MNs inside the spinal cord after both sensory and motor axons regenerate in the periphery.…”

Section: Discussionmentioning

confidence: 99%

“…Absence of Ia input implies that ventral horn motor circuitries operate after regeneration without feedback about muscles lengths and dynamics, and force signals from Ib Golgi afferents become unopposed, both affecting many spinal control mechanisms. Thus, motor tasks involving high forces and/or rapid and large muscle lengthening (steep slopes) show deficits (Abelew et al, 2000;Maas et al, 2007;Sabatier et al, 2011;Lyle et al, 2017;Chang et al, 2018). The mechanisms implicated in this die-back of ventral horn Ia axons are unknown.…”

Section: Introductionmentioning

confidence: 99%

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Spinal motor circuit synaptic plasticity after peripheral nerve injury depends on microglia activation and a CCR2 mechanism

et al. 2019

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Peripheral nerve injury results in persistent motor deficits, even after the nerve regenerates and muscles are reinnervated. This lack of functional recovery is partly explained by brain and spinal cord circuit alterations triggered by the injury, but the mechanisms are generally unknown. One example of this plasticity is the die-back in the spinal cord ventral horn of the projections of proprioceptive axons mediating the stretch reflex (Ia afferents). Consequently, Ia information about muscle length and dynamics is lost from ventral spinal circuits, degrading motor performance after nerve regeneration. Simultaneously, there is activation of microglia around the central projections of peripherally injured Ia afferents, suggesting a possible causal relationship between neuroinflammation and Ia axon removal. Therefore, we used mice (both sexes) that allow visualization of microglia (CX3CR1-GFP) and infiltrating peripheral myeloid cells (CCR2-RFP) and related changes in these cells to Ia synaptic losses (identified by VGLUT1 content) on retrogradely labeled motoneurons. Microgliosis around axotomized motoneurons starts and peaks within 2 weeks after nerve transection. Thereafter, this region becomes infiltrated by CCR2 cells, and VGLUT1 synapses are lost in parallel. Immunohistochemistry, flow cytometry, and genetic lineage tracing showed that infiltrating CCR2 cells include T cells, dendritic cells, and monocytes, the latter differentiating into tissue macrophages. VGLUT1 synapses were rescued after attenuating the ventral microglial reaction by removal of colony stimulating factor 1 from motoneurons or in CCR2 global KOs. Thus, both activation of ventral microglia and a CCR2-dependent mechanism are necessary for removal of VGLUT1 synapses and alterations in Ia-circuit function following nerve injuries. ) for the donation of the csf1-flox mouse line; and Myriam Alvarez for quantification of microglia in CSF1 motoneuron KOs.Synaptic plasticity and reorganization of essential motor circuits after a peripheral nerve injury can result in permanent motor deficits due to the removal of sensory Ia afferent synapses from the spinal cord ventral horn. Our data link this major circuit change with the neuroinflammatory reaction that occurs inside the spinal cord following injury to peripheral nerves. We describe that both activation of microglia and recruitment into the spinal cord of blood-derived myeloid cells are necessary for motor circuit synaptic plasticity. This study sheds new light into mechanisms that trigger major network plasticity in CNS regions removed from injury sites and that might prevent full recovery of function, even after successful regeneration.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spinal motor circuit synaptic plasticity after peripheral nerve injury depends on microglia activation and a CCR2 mechanism

et al. 2019

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“…Its absence, however, implies that ventral horn motor circuitries operate without Ia feedback about muscle lengths and dynamics after regeneration from nerve transections, thus affecting many critical spinal control mechanisms. Accordingly, motor tasks involving high forces and/or rapid and large muscle lengthening (steep slopes) show deficits (Abelew et al, 2000;Maas et al, 2007;Sabatier et al, 2011b;Lyle et al, 2017;Chang et al, 2018). Moreover, the lack of effective Ia inputs in the ventral horn might also affect circuitries like reciprocal inhibition and explain the presence of reciprocal excitation between antagonistic muscles and higher co-contraction and joint stiffness during motor function following regeneration from nerve transections (Sabatier et al, 2011a;Horstman et al, 2019; see Figure 10 in Horstman et al, 2019 for putative circuit mechanisms).…”

Section: Functional Consequences Of the Removal Of Ia Afferent Input mentioning

confidence: 99%

Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

Álvarez

Rotterman

Akhter

et al. 2020

Front. Mol. Neurosci.

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Motoneurons axotomized by peripheral nerve injuries experience profound changes in their synaptic inputs that are associated with a neuroinflammatory response that includes local microglia and astrocytes. This reaction is conserved across different types of motoneurons, injuries, and species, but also displays many unique features in each particular case. These reactions have been amply studied, but there is still a lack of knowledge on their functional significance and mechanisms. In this review article, we compiled data from many different fields to generate a comprehensive conceptual framework to best interpret past data and spawn new hypotheses and research. We propose that synaptic plasticity around axotomized motoneurons should be divided into two distinct processes. First, a rapid cell-autonomous, microglia-independent shedding of synapses from motoneuron cell bodies and proximal dendrites that is reversible after muscle reinnervation. Second, a slower mechanism that is microgliadependent and permanently alters spinal cord circuitry by fully eliminating from the ventral horn the axon collaterals of peripherally injured and regenerating sensory Ia afferent proprioceptors. This removes this input from cell bodies and throughout the dendritic tree of axotomized motoneurons as well as from many other spinal neurons, thus reconfiguring ventral horn motor circuitries to function after regeneration without direct sensory feedback from muscle. This process is modulated by injury severity, suggesting a correlation with poor regeneration specificity due to sensory and motor axons targeting errors in the periphery that likely render Ia afferent connectivity in the ventral horn nonadaptive. In contrast, reversible synaptic changes on the cell bodies occur only while motoneurons are regenerating. This cell-autonomous process displays unique features according to motoneuron type and modulation by local microglia and astrocytes and generally results in a transient reduction of fast synaptic activity that is probably replaced by embryonic-like slow GABA depolarizations, proposed to relate to regenerative mechanisms.

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“…However, even when successful, independent thumb and finger extension would be compromised. Tendon transfers in central nervous system disorders have been associated with modest results only (Coulet et al, 2022), possibly due to muscle–tendon plasticity and lack of spinal reflex circuitry reorganization (Lyle et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Selective transfer of nerve to supinator to restore digital extension in central cord syndrome: An anatomical study and a case report

et al. 2022

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Background Nerve transfers are increasingly used to restore upper extremity function in patients with spinal cord injury. However, the role of nerve transfers for central cord syndrome is still being established. The purpose of this study is to report the anatomical feasibility and clinical use of nerve transfer of supinator motor branches (NS) to restore finger extension in a central cord syndrome patient. Materials and Methods The posterior interosseous nerve (PIN), its superficial division, and branches were dissected in 14 fresh cadavers, with a mean age of 65 (58–79). Measurements included number and length of branches of donor and recipient, diameters, regeneration distance from coaptation site to motor entry point and axonal counts. A NS transfer to extensor carpi ulnaris (ECU), extensor digiti quinti (EDQ) and extensor digitorum communis (EDC) was performed in a 28‐year‐old patient, with central cord syndrome after a motorcycle accident, who did not recover active finger extension at 10 months post injury. Results The PIN consistently divided into a deep and superficial branch between 1.5 cm proximal to, and 2 cm distal to the distal boundary of the supinator. The superficial branch provided a first common branch to the ECU and EDQ. In 12/14 dissections, the EDC was innervated by a 4 cm long branch that entered the muscle on its radial deep surface. In all cases, the superficial branch of the PIN could be separated in a retrograde fashion from the PIN and coapted with NS. The mean myelinated fiber count in nerve to EDC was 401 ± 190 compared to 398 ± 75 in the NS. At 48 months after surgery, with the wrist at neutral, the patient recovered full metacarpophalangeal extension scoring M4. Supination was preserved with the elbow extended or flexed. Conclusions Restoration of finger extension in central cord syndrome is possible with a selective transfer of the NS to EDC, and is anatomically feasible with a short regeneration distance and favorable axonal count ratio.

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Musculotendon adaptations and preservation of spinal reflex pathways following agonist-to-antagonist tendon transfer

Cited by 5 publications

References 60 publications

Spinal motor circuit synaptic plasticity after peripheral nerve injury depends on microglia activation and a CCR2 mechanism

Spinal motor circuit synaptic plasticity after peripheral nerve injury depends on microglia activation and a CCR2 mechanism

Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

Selective transfer of nerve to supinator to restore digital extension in central cord syndrome: An anatomical study and a case report

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