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| Open AccessFully implanted battery-free high power platform for chronic spinal and muscular functional electrical stimulation
Electrical stimulation of the neuromuscular system holds promise for therapeutic biomedical applications, but is currently restricted by power. Here, the authors introduce fully implantable resonator-based designs achieving ±20 V compliance and >300 mW output, enabling multichannel, biphasic, current-controlled operation to evoke functional gate patterns for 6-weeks in freely behaving rats.
- Alex Burton
- , Zhong Wang
- & Philipp Gutruf
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| Open AccessRole of TMEM100 in mechanically insensitive nociceptor un-silencing
Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.
- Timo A. Nees
- , Na Wang
- & Stefan G. Lechner
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| Open AccessIntrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals
Muscle spindles sense muscle tension to coordinate body movement. This paper reveals a mechanism of spindle formation and maintenance and to better understanding changes in movement in muscle disorders and ageing.
- Rangjuan Cao
- , Peng Chen
- & Lin Mei
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| Open AccessSynchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain
Increased low frequency cortical oscillations are observed in neuropathic pain. Here the authors perform Ca2+ imaging of DRG sensory neurons in a mouse model of neuropathic pain, and show that synchronized activity of DRG neurons occurs within hours after injury and 1-2 days before increased cortical oscillations are observed.
- Chao Chen
- , Linlin Sun
- & Peifu Tang
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Article
| Open AccessAAV2/9-mediated silencing of PMP22 prevents the development of pathological features in a rat model of Charcot-Marie-Tooth disease 1 A
Charcot-Marie-Tooth disease 1 A (CMT1A) results from PMP22 gene duplication and is characterized by peripheral nerve myelination deficits. Here, the authors prevent the development of pathological features in a rat model of CMT1A through the local delivery of AAV2/9 expressing shRNAs against PMP22.
- Benoit Gautier
- , Helene Hajjar
- & Nicolas Tricaud
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| Open AccessSingle cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain
The contribution of distinct types of dorsal root ganglion neurons to chronic pain is unclear. Here, the authors molecularly profile non-human primate sensory neurons and show that genome-wide associations converge on two neuronal types with different genetic susceptibilities for chronic pain.
- Jussi Kupari
- , Dmitry Usoskin
- & Patrik Ernfors
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Article
| Open AccessMolecular correlates of muscle spindle and Golgi tendon organ afferents
Coordinated movement critically depends on sensory feedback from muscle spindles (MSs) and Golgi tendon organs (GTOs) but the afferents supplying this proprioceptive feedback have remained genetically inseparable. Here the authors use single cell transcriptome analysis to reveal the molecular basis of MS (groups Ia and II) and GTO (group Ib) afferent identities in the mouse.
- Katherine M. Oliver
- , Danny M. Florez-Paz
- & Joriene C. de Nooij
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| Open AccessOrgan-specific, multimodal, wireless optoelectronics for high-throughput phenotyping of peripheral neural pathways
Advances in wireless technologies have enabled internalisation of light sources, but organ specific illumination is challenging. Here, the authors present a durable, multimodal, wireless system enabling optogenetic stimulation of peripheral neurons within organs.
- Woo Seok Kim
- , Sungcheol Hong
- & Sung Il Park
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Article
| Open AccessImaging fascicular organization of rat sciatic nerves with fast neural electrical impedance tomography
To be successful, selective neuromodulation requires a non-invasive method of imaging the fascicular anatomy of peripheral nerves. Here, the authors show the applicability and reliability of fast neural electrical impedance tomography for this purpose and provide its validation against the gold standards of invasive imaging.
- Enrico Ravagli
- , Svetlana Mastitskaya
- & David Holder
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Article
| Open AccessTRPV4 disrupts mitochondrial transport and causes axonal degeneration via a CaMKII-dependent elevation of intracellular Ca2+
Mutations in the TRPV4 channel cause inherited neurodegeneration syndromes, but the molecular mechanisms are unknown. Here the authors reveal that TRPV4 activation causes dose-dependent, CaMKII-mediated neuronal dysfunction and axonal degeneration via disruption of mitochondrial axonal transport.
- Brian M. Woolums
- , Brett A. McCray
- & Thomas E. Lloyd
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Article
| Open AccessActive acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation
Denervation of muscle fibres induces muscle atrophy, via mechanisms that remain unclear. Here, the authors show that binding of acetylcoline to its receptor at the neuromuscular junction represses the expression of connexins 43 and 45, which promote atrophy, and is sufficient to prevent denervation-induced loss of myofibre mass.
- Bruno A. Cisterna
- , Aníbal A. Vargas
- & Juan C. Sáez
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Article
| Open AccessmTORC1 and PKB/Akt control the muscle response to denervation by regulating autophagy and HDAC4
Denervation leads to muscle atrophy and neuromuscular endplate remodeling. Here, the authors show that a balanced activation of mTORC1 contributes to the dynamic regulation of autophagic flux in denervated muscle and that activation of PKB/Akt promotes the nuclear import of HDAC4, which is essential for endplate maintenance upon nerve injury
- Perrine Castets
- , Nathalie Rion
- & Markus A. Rüegg
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Article
| Open AccessLong-term imaging of dorsal root ganglia in awake behaving mice
Imaging sensory neurons in the dorsal root ganglion (DRG) in awake animals is challenging due to motion artefacts and other technical issues. Here the authors develop an intervertebral fusion procedure which minimizes spinal movement thereby enabling chronic imaging of DRG neurons in awake, behaving mice.
- Chao Chen
- , Jinhui Zhang
- & Guang Yang