Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity

Brandt, Jaclyn; Evans, Jonathan; Mildenhall, Taylor; Mulligan, Amanda; Konieczny, Aimee; Rose, Samuel J.; English, Arthur W.

doi:10.1152/jn.00892.2014

Cited by 29 publications

(43 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this same context, medium and large DRG neurons are primarily responsible for proprioceptive feedback and mechanosensation, while small DRG neurons are largely nociceptive. We (Brandt et al ., ; Cannoy et al ., ) and others (Cope et al ., ; Lyle et al ., ) have argued previously that restoration of the impact of the larger afferent neurons is an important factor in improving functional recovery after peripheral nerve injury. The promotion of regeneration of presumed proprioceptive axons by selective afferent stimulation is thus encouraging.…”

Section: Discussionmentioning

confidence: 98%

Optogenetically enhanced axon regeneration: motor versus sensory neuron‐specific stimulation

Ward

Clanton

English

2018

Eur J of Neuroscience

Self Cite

View full text Add to dashboard Cite

Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluate the precision and selectivity of system-specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light-sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons had regenerated successfully was greater following system-specific optical treatment, with no effect on the number of ChR2-negative neurons (whether motor or sensory neurons). We conclude that acute system-specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration-enhancing effect is likely cell autonomous.

show abstract

Section: Discussionmentioning

confidence: 98%

Optogenetically enhanced axon regeneration: motor versus sensory neuron‐specific stimulation

Ward

Clanton

English

2018

Eur J of Neuroscience

Self Cite

View full text Add to dashboard Cite

show abstract

“…In rats with peripheral nerve transection, which are stimulated by means of treadmill exercise, Ia terminals reveal ability to reinnervate MN soma, correlating with restoration of H-reflex in exercised rats [60, 61]. The contribution of Ia terminals on dendrites in this restoration is not known, but the studies we quote indicate that somatic subpopulation of Ia terminals contributes significantly to motoneuron functional states [51,57,58].…”

Section: Discussionmentioning

confidence: 99%

Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons

et al. 2016

View full text Add to dashboard Cite

The effects of stimulation of low-threshold proprioceptive afferents in the tibial nerve on two types of excitatory inputs to α-motoneurons were tested. The first input is formed by glutamatergic Ia sensory afferents contacting monosynaptically α-motoneurons. The second one is the cholinergic input originating from V0c—interneurons, located in lamina X of the spinal cord, modulating activity of α-motoneurons via C-terminals. Our aim was to clarify whether enhancement of signaling to ankle extensor α-motoneurons, via direct electrical stimulation addressed predominantly to low-threshold proprioceptive fibers in the tibial nerve of awake rats, will affect Ia glutamatergic and cholinergic innervation of α-motoneurons of lateral gastrocnemius (LG). LG motoneurons were identified with True Blue tracer injected intramuscularly. Tibial nerve was stimulated for 7 days with continuous bursts of three pulses applied in four 20 min sessions daily. The Hoffmann reflex and motor responses recorded from the soleus muscle, LG synergist, allowed controlling stimulation. Ia terminals and C-terminals abutting on LG-labeled α-motoneurons were detected by immunofluorescence (IF) using input-specific anti- VGLUT1 and anti-VAChT antibodies, respectively. Quantitative analysis of confocal images revealed that the number of VGLUT1 IF and VAChT IF terminals contacting the soma of LG α-motoneurons increased after stimulation by 35% and by 26%, respectively, comparing to the sham-stimulated side. The aggregate volume of VGLUT1 IF and VAChT IF terminals increased by 35% and by 30%, respectively. Labeling intensity of boutons was also increased, suggesting an increase of signaling to LG α-motoneurons after stimulation. To conclude, one week of continuous burst stimulation of proprioceptive input to LG α-motoneurons is effective in enrichment of their direct glutamatergic but also indirect cholinergic inputs. The effectiveness of such and longer stimulation in models of injury is a prerequisite to propose it as a therapeutic method to improve inputs to selected group of α-motoneurons after damage.

show abstract

“…The vesicular glutamate transporter 1-positive synaptic inputs emanating from group Ia afferent neurons are normally with-drawn permanently and the inhibitory glutamate decarboxylase 67positive inputs are normally withdrawn transiently following peripheral transection Rotterman et al, 2014). These synaptic inputs were retained on and/or restored onto the motoneurons 10 weeks later by the sex-specific exercise programs of continuous and interval training for 2 weeks in male and female rats, respectively (Liu et al, 2014;Brandt et al, 2015) (Fig. 9).…”

Section: Exercise With and Without Es Promotes Nerve Regenerationmentioning

confidence: 97%

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

Gordon

English

2015

Eur J of Neuroscience

Self Cite

244

194

View full text Add to dashboard Cite

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use.

show abstract

Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity

Abstract: Brandt J, Evans JT, Mildenhall T, Mulligan A, Konieczny A, Rose SJ, English AW. Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity.

Cited by 29 publications

References 51 publications

Optogenetically enhanced axon regeneration: motor versus sensory neuron‐specific stimulation

Optogenetically enhanced axon regeneration: motor versus sensory neuron‐specific stimulation

Electrical Stimulation of Low-Threshold Proprioceptive Fibers in the Adult Rat Increases Density of Glutamatergic and Cholinergic Terminals on Ankle Extensor α-Motoneurons

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

Contact Info

Product

Resources

About