Asymptotic construction of pulses in the Hodgkin Huxley model for myelinated nerves

A quantitative description of pulses and wave trains in the spatially discrete Hodgkin-Huxley model for myelinated nerves is given. Predictions of the shape and speed of the waves and the thresholds for propagation failure are obtained. Our asymptotic predictions agree quite well with numerical solutions of the model and describe wave patterns generated by repeated firing at a boundary.Comment: to appear in Phys. Rev.

Glial βii spectrin contributes to paranode formation and maintenance

Action potential conduction along myelinated axons depends on high densities of voltage-gated Na channels at the nodes of Ranvier. Flanking each node, paranodal junctions (paranodes) are formed between axons and Schwann cells in the peripheral nervous system (PNS) or oligodendrocytes intheCNS. Paranodal junctions contribute to both no deassembly and maintenance. Despitetheir importance, the molecular mechanisms responsible for paranode assembly and maintenance remain poorly understood. βII spectrin is expressed in diverse cells and is an essential part of the submembranous cytoskeleton. Here, we show that Schwann cell βII spectrin is highly enriched at paranodes. To elucidate the roles of glial βII spectrin, we generated mutant mice lacking βII spectrin in myelinating glial cells by crossing mice with a floxed allele of Sptbn1 with Cnp-Cre mice, and analyzed both male and female mice. Juvenile (4 weeks) and middle-aged (60 weeks) mutant mice showed reduced grip strength and sciatic nerve conduction slowing, whereas no phenotype was observed between 8 and 24 weeks of age. Consistent with these findings, immunofluorescence microscopy revealed disorganized paranodes in the PNS and CNS of both postnatal day 13 and middle-aged mutant mice, but not in young adult mutant mice. Electron microscopy confirmed partial loss of transverse bands at the paranodal axoglial junction in the middle-aged mutant mice in both the PNS and CNS. These findings demonstrate that a spectrin-based cytoskeleton in myelinating glia contributes to formation and maintenance of paranodal junctions.Fil: Susuki, Keiichiro. Baylor College of Medicine; Estados UnidosFil: Zollinger, Daniel R.. Baylor College of Medicine; Estados UnidosFil: Chang, Kae Jiun. Baylor College of Medicine; Estados UnidosFil: Zhang, Chuansheng. Baylor College of Medicine; Estados UnidosFil: Huang, Claire Yu Mei. Baylor College of Medicine; Estados UnidosFil: Tsai, Chang Ru. Baylor College of Medicine; Estados UnidosFil: Galiano, Mauricio Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina. Baylor College of Medicine; Estados UnidosFil: Liu, Yanhong. Baylor College of Medicine; Estados UnidosFil: Benusa, Savannah D.. Virginia Commonwealth University; Estados UnidosFil: Yermakov, Leonid M.. Wright State University; Estados UnidosFil: Griggs, Ryan B.. Wright State University; Estados UnidosFil: Dupree, Jeffrey L.. Virginia Commonwealth University; Estados UnidosFil: Rasband, Matthew N.. Baylor College of Medicine; Estados Unido

Pulse propagation in discrete systems of coupled excitable cells

Propagation of pulses in myelinated fibers may be described by appropriate solutions of spatially discrete FitzHugh-Nagumo systems. In these systems, propagation failure may occur if either the coupling between nodes is not strong enough or the recovery is too fast. We give an asymptotic construction of pulses for spatially discrete FitzHugh-Nagumo systems which agrees well with numerical simulations and discuss evolution of initial data into pulses and pulse generation at a boundary. Formulas for the speed and length of pulses are also obtained.Comment: 16 pages, 10 figures, to appear in SIAM J. Appl. Mat

Nodes, paranodes and neuropathies

This review summarises recent evidence supporting the involvement of the specialised nodal and perinodal domains (the paranode and juxtaparanode) of myelinated axons in the pathology of acquired, inflammatory, peripheral neuropathies.The identification of new target antigens in the inflammatory neuropathies heralds a revolution in diagnosis, and has already begun to inform increasingly targeted and individualised therapies. Rapid progress in our basic understanding of the highly specialised nodal regions of peripheral nerves serves to strengthen the links between their unique microstructural identities, functions and pathologies. In this context, the detection of autoantibodies directed against nodal and perinodal targets is likely to be of increasing clinical importance. Antiganglioside antibodies have long been used in clinical practice as diagnostic serum biomarkers, and associate with specific clinical variants but not to the common forms of either acute or chronic demyelinating autoimmune neuropathy. It is now apparent that antibodies directed against several region-specific cell adhesion molecules, including neurofascin, contactin and contactin-associated protein, can be linked to phenotypically distinct peripheral neuropathies. Importantly, the immunological characteristics of these antibodies facilitate the prediction of treatment responsiveness

Pinning and propagation in spatially discrete bistable systems

Depto. de Análisis Matemático y Matemática AplicadaFac. de Ciencias MatemáticasFALSEunpu

Pathological classification of equine recurrent laryngeal neuropathy

Recurrent Laryngeal Neuropathy (RLN) is a highly prevalent and predominantly left‐sided, degenerative disorder of the recurrent laryngeal nerves (RLn) of tall horses, that causes inspiratory stridor at exercise because of intrinsic laryngeal muscle paresis. The associated laryngeal dysfunction and exercise intolerance in athletic horses commonly leads to surgical intervention, retirement or euthanasia with associated financial and welfare implications. Despite speculation, there is a lack of consensus and conflicting evidence supporting the primary classification of RLN, as either a distal (“dying back”) axonopathy or as a primary myelinopathy and as either a (bilateral) mononeuropathy or a polyneuropathy; this uncertainty hinders etiological and pathophysiological research. In this review, we discuss the neuropathological changes and electrophysiological deficits reported in the RLn of affected horses, and the evidence for correct classification of the disorder. In so doing, we summarize and reveal the limitations of much historical research on RLN and propose future directions that might best help identify the etiology and pathophysiology of this enigmatic disorder

The effects of non-focused extracorporeal shock waves on neuronal morphology, function and analgesia in horses

These studies were conducted to elucidate the regional analgesic effect that is observed clinically after treatment of orthopedic disorders with application of extracorporeal shock waves in horses. Regional analgesia after treatment with extracorporeal shock waves presents a concern because it may eliminate protective limiting mechanisms and may place equine athletes with predisposing lesions at risk of sustaining career- or life-ending injuries. Direct percutaneous application of non-focused extracorporeal shock waves to palmar digital nerves in the pastern area of horses resulted in decreased sensory nerve conduction velocities compared with untreated control nerves at 3, 7, and 35 days after treatment. Transmission electron microscopy revealed distinct morphological changes consisting of extensive separation and disruption between the different layers of the myelin sheath in large- to medium-sized myelinated axons of treated palmar digital nerves. Treatment of selected areas of the metacarpus in horses with non-focused extracorporeal shock waves failed to identify a regional analgesic effect when cutaneous sensation was assessed by comparing the nociceptive threshold (limb withdrawal reflex latency, LWRL) between treated and non-treated areas after stimulation with a focused light source. The LWRL responses in all horses were comparable in treated and control areas over time with a significant decrease noted at most sites and time points compared with baseline values

Real-Time CARS Imaging Reveals a Calpain-Dependent Pathway for Paranodal Myelin Retraction during High-Frequency Stimulation

High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down