Peripheral nervous system articles within Nature Communications

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  • Article
    | Open Access

    Previous work has shown that natural cardiac rhythms modulate the perception and reaction to sensory cues through changes in associated neural signals. Here, the authors show that sensitivity to prediction errors during reward learning is related to the phase of the cardiac cycle.

    • Elsa F. Fouragnan
    • , Billy Hosking
    •  & Alejandra Sel

  • Article
    | Open Access

    Neurostimulators are often bulky and uncomfortable. Researchers report a wireless, leadless, and battery-free ultrasound receiver that wraps around the target peripheral nerve and allows precise modulation of organ function, providing a framework for future bioelectronic medicines

    • Tong Li
    • , Zhidong Wei
    •  & Zhang-Qi Feng

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Coagulation factor VIII deficiency in hemophilia A disrupts clotting and prolongs bleeding. Here, the authors show that vagus nerve stimulation bypasses this defect and improves hemostasis in hemophilia A mice through a mechanism requiring acetylcholine-secreting ChAT+ T lymphocytes in spleen and α7nAChR on circulating platelets.

    • Carlos E. Bravo-Iñiguez
    • , Jason R. Fritz
    •  & Jared M. Huston

  • Article
    | Open Access

    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

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Sympathetic neurons are affected in familial dysautonomia, a rare disease associated with a mutation in ELP1, but the mechanisms are not fully understood. Here the authors show, using neurons derived from participants with familial dysauotnomia, that spontaneous sympathetic neuron hyperactivity is observed and is associated with norepinephrine transporter deficits.

    • Hsueh-Fu Wu
    • , Wenxin Yu
    •  & Nadja Zeltner

  • Article
    | Open Access

    The autonomic nervous systems densely innervate the pancreas, but its contribution to pancreatic ductal adenocarcinoma (PDAC) progression is not fully understood. Here, the authors characterize the pattern of sympathetic innervation by 3D imaging in a murine model of PDAC and show that sympathectomy aggravates cancer progression.

    • Jérémy Guillot
    • , Chloé Dominici
    •  & Fanny Mann

  • Article
    | Open Access

    Soft tissue trauma can result in aberrant osteochondral differentiation of local mesenchymal progenitor cells. Here the authors show that, in mice, soft tissue trauma results in NGF expression by perivascular cells, which leads to axonal invasion and drives abnormal osteochondral differentiation, and show that this process can be prevented by inhibition of NGF signaling.

    • Seungyong Lee
    • , Charles Hwang
    •  & Benjamin Levi

  • Article
    | Open Access

    Many animals, including mammals and insects, like slightly acidic yet dislike highly acidic foods, but how animals discriminate low from high acidity is unclear. Here the authors demonstrate that the fruit fly uses an evolutionarily conserved taste receptor to distinguish low from high concentrations of acid.

    • Tingwei Mi
    • , John O. Mack
    •  & Yali V. Zhang

  • Article
    | Open Access

    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

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Hypothalamic melanocortin neurons regulate systemic glucose homeostasis through incompletely understood pathways. Here, the authors show that a subset of pro-opiomelanocortin neurons innervate the liver via preganglionic parasympathetic cholinergic neurons in the dorsal motor nucleus of the vagus and that stimulation of this pathway elevates blood glucose levels

    • Eunjin Kwon
    • , Hye-Young Joung
    •  & Young-Hwan Jo

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Neurofibromatosis type I (NF1) is characterized by prominent skeletal abnormalities mediated in part by aberrant ERK pathway activation due to NF1 loss-of-function. Here, the authors report the MEKK2 is a key mediator of this aberrant ERK activation and that MEKK2 inhibitors, including ponatinib, ameliorate skeletal defects in a mouse model of NF1.

    • Seoyeon Bok
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt

  • Article
    | Open Access

    The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.

    • Stefanie Fenske
    • , Konstantin Hennis
    •  & Christian Wahl-Schott

  • Article
    | Open Access

    The contribution of satellite glia to peripheral nerve regeneration is unclear. Here, the authors show that satellite glia are transcriptionally distinct from Schwann cells, share similarities with astrocytes, and, upon injury, they contribute to axon regeneration via Fasn-PPARα signalling pathway.

    • Oshri Avraham
    • , Pan-Yue Deng
    •  & Valeria Cavalli

  • Article
    | Open Access

    Modulation of peripheral nervous system signalling has many applications in medicine, neurobiology and machine-man interfaces. Here the authors develop a microscale implantable device for chronic interfacing with a small diameter nerve, and show multi-week in vivo recording and control of activity.

    • Timothy M. Otchy
    • , Christos Michas
    •  & Timothy J. Gardner

  • Article
    | Open Access

    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

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Autonomic dysfunction is a feature of some α-synucleinopathies, but there are no models of pure autonomic dysfunction associated with α-synuclein. Here the authors describe a mouse model of pure autonomic dysfunction without motor dysfunciton by injection of pre-formed fibrils of α-synuclein to the stellate and celiac ganglia.

    • Xue-Jing Wang
    • , Ming-Ming Ma
    •  & Xue-Bing Ding

  • Article
    | Open Access

    The extracellular regions (ECRs) of adhesion GPCRs have diverse biological functions, but their structures and mechanisms of action remain unclear. Here, the authors solve the ECR structure of the Gpr126 receptor and show that ECR conformation and signaling functions are regulated by alternative splicing.

    • Katherine Leon
    • , Rebecca L. Cunningham
    •  & Demet Araç

  • Article
    | Open Access

    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

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The wiring of peripheral neural circuits that regulate heart rate is poorly understood. In this study, authors used tissue clearing for high-resolution characterization of nerves in the heart in 3D and transgenic and novel viral vector approaches to identify peripheral parasympathetic and sympathetic neuronal populations involved in heart rate control in mice.

    • Pradeep S. Rajendran
    • , Rosemary C. Challis
    •  & Kalyanam Shivkumar

  • Article
    | Open Access

    Diagnosis and classification of peripheral neuropathy (PN) is facilitated by nerve conduction (NC) studies. Here, Bjornsdottir et al. find a low-frequency PRPH splice-donor variant that associates with NC amplitude and neurological assessment of recalled PRPH variant carriers reveals increased risk of a mild sensory-negative PN.

    • Gyda Bjornsdottir
    • , Erna V. Ivarsdottir
    •  & Kari Stefansson

  • Article
    | Open Access

    Stimulation of peripheral nerve activity may be used to treat metabolic and inflammatory disorders, but current approaches need implanted devices. Here, the authors present a non-invasive approach, and show that ultrasound-mediated stimulation can be targeted to specific sub-organ locations in preclinical models and alter the response of metabolic and inflammatory neural pathways.

    • Victoria Cotero
    • , Ying Fan
    •  & Christopher Puleo

  • Article
    | Open Access

    Transcranial alternating current stimulation (tACS) uses weak electrical currents, applied to the head, to modulate brain activity. Here, the authors show that contrary to previous assumptions, the effects of tACS on the brain may be mediated by its effect on peripheral nerves in the skin, not direct.

    • Boateng Asamoah
    • , Ahmad Khatoun
    •  & Myles Mc Laughlin

  • Article
    | Open Access

    Axons of the peripheral nervous system regenerate along Schwann cells following injury. Here, the authors show that regenerating axons follow pioneer axons and this process is mediated by lipoprotein receptor-related protein 4 (Lrp4), a protein otherwise known for its role in synapse formation.

    • Katherine D. Gribble
    • , Lauren J. Walker
    •  & Michael Granato

  • Article
    | Open Access

    Hematopoietic sites in theDrosophilalarva require the local peripheral nervous system for blood cells (hemocytes) to survive and proliferate, but how this is mediated is unclear. Here, the authors identify Activin-β from sensory neurons as signalling to hemocytes, affecting proliferation and adhesion.

    • Kalpana Makhijani
    • , Brandy Alexander
    •  & Katja Brückner

  • Article
    | Open Access

    Demonstrating a causal relationship between cardiac vagal tone and exercise capacity has been previously limited by methodological constraints. Using genetic targeting, silencing and optogenetic recruitment of vagal motor neuron activity in rodents, Machhadaet al. provide direct evidence that vagal drive determines the ability to exercise.

    • Asif Machhada
    • , Stefan Trapp
    •  & Alexander V. Gourine

  • Article
    | Open Access

    Diphtheria toxin selectively kills cells engineered to express the diphtheria toxin receptor (DTR). Here the authors report a PEGylated version of diphtheria toxin that does not enter the brain, allowing for ablation of only peripheral cells when using Cre lines that drive DTR expression in both the periphery and in the brain.

    • Mafalda M. A. Pereira
    • , Inês Mahú
    •  & Ana I. Domingos

  • Article
    | Open Access

    Microglia and monocytes contribute to neuropathic pain states, but the precise role of the two cell types is not clear. Here Peng et al.use temporally controlled ablation of monocytes and microglia in mice to show that these cells work together to initiate neuropathic-pain like behaviour, but are less important in the maintenance phase.

    • Jiyun Peng
    • , Nan Gu
    •  & Long-Jun Wu

  • Article
    | Open Access

    The enteric nervous system (ENS) plays a key role in regulating gut motility and homeostasis yet it remains a challenging system to record from. Here, the authors develop a novel abdominal window permitting simultaneous optical and electrical recording of mouse ENS system activity over prolonged time periods.

    • Nikolai Rakhilin
    • , Bradley Barth
    •  & Xiling Shen

  • Article
    | Open Access

    The evolutionary origin of the peripheral nervous systems (PNSs) is poorly understood. Here, the authors show that two mechanisms activate gene circuits in ascidians to differentiate epidermal sensory neurons, which suggests that vertebrate PNSs arose via cooption of the ancient PNS gene circuit.

    • Kana Waki
    • , Kaoru S. Imai
    •  & Yutaka Satou

  • Article
    | Open Access

    MicroRNAs are known to regulate myelination in the peripheral nervous system, but the underlying mechanisms remain unclear. Here the authors show that the Lin28B/let-7 axis drives the onset of myelination by promoting Krox20 expression through suppression of Notch signalling.

    • Deniz Gökbuget
    • , Jorge A. Pereira
    •  & Ueli Suter

  • Article |

    The segmentation motor activity of the small intestine is believed to be a result of alternating inhibitory and excitatory neural activity. Huizinga et al.show that the segmentation motor pattern is in fact a result of phase–amplitude interactions of slow-wave activities generated by two networks of interstitial cells of Cajal.

    • Jan D. Huizinga
    • , Ji-Hong Chen
    •  & David Chen

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