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(A) Cartoon illustrating the structures of the myelinated nerve fiber and axonal subdomains: AIS, nodes of Ranvier (N), paranode (PN), and juxtaparanodes (JP). (B) Longitudinal sections of mouse optic nerve section immunostained with antibodies to Nav channels (nodal marker, red), Caspr (paranodal marker, green), and Kv1.2 channels (juxtaparanodal marker, blue). (C) Schematic presentation showing molecular organization at nodes, paranodes, and juxtaparanodes, and proposed three complementary mechanisms for node assembly. Gliomedin is the ECM component in the PNS that interacts with NF186. Paranodal junctions (PJ) restrict the mobility of membrane molecular complexes at nodes or juxtaparanodes. Cytoskeletal scaffolds (CS) further stabilize the Nav channel complex at nodes.
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Dysfunction and/or disruption of nodes of Ranvier are now recognized as key contributors to the pathophysiology of various neurological diseases. One reason is that the excitable nodal axolemma contains a high density of voltage-gated Na+ channels that are required for the rapid and efficient saltatory conduction of action potentials. Nodal physiol...
Contexts in source publication
Context 1
... are highly polarized cells and the myelinated ax- ons are divided into multiple distinct membrane domains including AIS (axon initial segments), nodes of Ranvier, para- nodes, juxtaparanodes, internodes, and terminals ( Figure 1A). Specific molecular complexes characterize each of these do- mains ( Figures 1B and 1C) [for more detail, see (Poliak and Peles, 2003;Salzer, 2003;Rasband, 2011)]. ...Context 2
... are highly polarized cells and the myelinated ax- ons are divided into multiple distinct membrane domains including AIS (axon initial segments), nodes of Ranvier, para- nodes, juxtaparanodes, internodes, and terminals ( Figure 1A). Specific molecular complexes characterize each of these do- mains ( Figures 1B and 1C) [for more detail, see (Poliak and Peles, 2003;Salzer, 2003;Rasband, 2011)]. The AIS share a common molecular organization with nodes of Ranvier (Rasband, 2010). ...Context 3
... the flanking paranodes, axonal contactin and Caspr (contactin-associated protein) and glial NF155 form a tripartite cell adhesion molecule complex that mediates the assembly of the septate-like junctions between the myelin sheath and the axon. Three mechanisms operate conjointly during nodal assembly: (1) clustering of NF186 by a glia- derived ECM (extracellular matrix), (2) restriction of nodal membrane protein mobility by paranodal junctions, and (3) stabilization of Nav channels by axonal cytoskeletal scaffolds ( Figure 1C) (Susuki and Rasband, 2008). There are some dif- ferences in the molecular organization and assembly mech- anisms between PNS and CNS nodes. ...Context 4
... the three mechanisms described above, the ECM is the primary one in the PNS ( Feinberg et al., 2010;Susuki et al., 2013), whereas paranodes drive nodal assembly in the CNS ( Susuki et al., 2013). Juxtaparanodes flank paranodes and reside un- der the myelin sheaths ( Figure 1C). Juxtaparanodal molecules include Kv1 channels, Caspr2, and Tag1 (transiently expressed axonal glycoprotein 1). ...Context 5
... addition to gangliosides, some studies have identified autoantibodies against nodal, paranodal, or juxtaparanodal proteins in sera from patients with autoimmune neurolog- ical diseases. A small portion of patients with GBS or CIDP (chronic inflammatory demyelinating polyradiculoneuropa- thy) had autoantibodies to gliomedin, NF186, NF155, con- tactin, or contactin/Caspr complex (for protein localization, see Figure 1C) (Prüss et al., 2011;Devaux et al., 2012;Ng et al., 2012;Querol et al., 2013). The pathogenic roles of these autoantibodies in human patients have yet to be tested (Hughes and Willison, 2012). ...Context 6
... antibody to pan-NF administered to the animals with EAE (experimental allergic encephalomyelitis), an animal model for MS, bound selectively at nodes of Ranvier in spinal cords together with complement, induced acute axonal injury, and exacerbated the clinical disease ( Mathey et al., 2007). In addition, anti- bodies to βIV spectrin, a submembranous cytoskeletal protein located in AIS and in nodes of Ranvier ( Figure 1C), were de- tected in a patient with paraneoplastic lower motor neuron syndrome associated with breast cancer ( Berghs et al., 2001). After the removal of the cancer, the titer of the autoanti- bodies and binding at AIS drastically reduced, and neurologi- cal symptoms partially improved, suggesting an autoimmune mechanism for the disease. ...Context 7
... autoanti- bodies against nodal and paranodal proteins may cause Nav channel dysfunction similar to the situation in AMAN. Fur- thermore, since these molecules are involved in the formation and stabilization of Nav channel clusters at nodes (see Fig- ure 1C), their disruption may adversely impact node assembly and/or maintenance; consequently destabilizing nodal Nav channels and thereby damaging neural transmission. ...Context 8
... the Trembler-J heminodes and nodes contain two unusual ion channel subtypes: Nav1.8 and Kv3.1b. Nav1.8 is a tetrodotoxin-resistant Nav channel subtype normally expressed in nociceptive sensory neurons and may have important roles in pain [reviewed in (Eijkelkamp et al., 2012)], but is not usually detected at nodes (Devaux and Scherer, 2005). Kv3.1b is detected at CNS, al- though usually not PNS, nodes where it may participate in the repolarization of the axon (Devaux et al., 2003). ...Citations
... White matter disruption is a prominent feature observed in many neurological disorders through neuroimaging (Guimaraes et al. 2009;Davenport et al. 2012) as well as from pathological studies (Chen et al. 2021;Xu et al. 2022) Correspondingly, demyelination and axonal degeneration are the foremost pathologies, along with disruption or dysfunction of NoR being a critical factor in some PNS and CNS-related diseases (Susuki 2013). The alteration in the nodal environment, demyelination, axonal disruption, and white matter degeneration are all suggested to be mediated by direct or indirect disruption of axo-glial interactions (Faivre-Sarrailh and Devaux 2013). ...
... And numerous CNS disorders stated above deal with hampered or loss of axonal conduction. Hence, these channels have a massive impact on modulating neuronal excitability in various CNS disorders such as epilepsy, autism, and ALS (Susuki 2013). Also, autoantibodies produced against the nodal components, as described in MS and GBS, attack the nodal proteins and disrupt the integrity of the axo-glial junction (Susuki et al. 2012). ...
The action potential conduction along the axon is highly dependent on the healthy interactions between the axon and myelin-producing glial cells. Myelin, which facilitates action potential, is the protective insulation around the axon formed by Schwann cells and oligodendrocytes in the peripheral (PNS) and central nervous system (CNS), respectively. Myelin is a continuous structure with intermittent gaps called nodes of Ranvier, which are the sites enriched with ion channels, transmembrane, scaffolding, and cytoskeletal proteins. Decades-long extensive research has identified a comprehensive proteome with strictly regularized localization at the node of Ranvier. Concurrently, axon-glia interactions at the node of Ranvier have gathered significant attention as the pathophysiological targets for various neurodegenerative disorders. Numerous studies have shown the alterations in the axon-glia interactions culminating in neurological diseases. In this review, we have provided an update on the molecular composition of the node of Ranvier. Further, we have discussed in detail the consequences of disruption of axon-glia interactions during the pathogenesis of various CNS and PNS disorders.
Graphical Abstract
... Anatomy and molecular organization of the myelinated fiber. Associations between the localization and type of polyneuropathy and specific site of neuronal damage according to[41,[56][57][58]. ...
The spectrum of immune-mediated neuropathies is broad and the different subtypes are still being researched. With the numerous subtypes of immune-mediated neuropathies, establishing the appropriate diagnosis in normal clinical practice is challenging. The treatment of these disorders is also troublesome. The authors have undertaken a literature review of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), Guillain–Barre syndrome (GBS) and multifocal motor neuropathy (MMN). The molecular, electrophysiological and ultrasound features of these autoimmune polyneuropathies are analyzed, highlighting the differences in diagnosis and ultimately treatment. The immune dysfunction can lead to damage to the peripheral nervous system. In practice, it is suspected that these disorders are caused by autoimmunity to proteins located in the node of Ranvier or myelin components of peripheral nerves, although disease-associated autoantibodies have not been identified for all disorders. The electrophysiological presence of conduction blocks is another important factor characterizing separate subgroups of treatment-naive motor neuropathies, including multifocal CIDP (synonyms: multifocal demyelinating neuropathy with persistent conduction block), which differs from multifocal motor neuropathy with conduction block (MMN) in both responses to treatment modalities and electrophysiological features. Ultrasound is a reliable method for diagnosing immune-mediated neuropathies, particularly when alternative diagnostic examinations yield inconclusive results. In overall terms, the management of these disorders includes immunotherapy such as corticosteroids, intravenous immunoglobulin or plasma exchange. Improvements in clinical criteria and the development of more disease-specific immunotherapies should expand the therapeutic possibilities for these debilitating diseases.
... Different pathomechanisms involve axonal, myelin and Schwann cell damage. In recent years, the essential role of the node of Ranvier and the severe consequences of its alterations have come to focus (Susuki, 2013;Uncini et al., 2013). ...
The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical reconstruction microscopy (dSTORM) and supported our data by high-content confocal imaging combined with deep learning-based analysis. As a result, we revealed a ~ 190 nm periodic protein arrangement of cytoskeletal proteins and axoglial cell adhesion molecules in human peripheral nerves. In patients with polyneuropathy, periodic distances increased at the paranodal region of the node of Ranvier, both at the axonal cytoskeleton and at the axoglial junction. In-depth image analysis revealed a partial loss of proteins of the axoglial complex (Caspr-1, neurofascin-155) in combination with detachment from the cytoskeletal anchor protein ß2-spectrin. High content analysis showed that such paranodal disorganization occurred especially in acute and severe axonal neuropathy with ongoing Wallerian degeneration and related cytoskeletal damage. We provide nanoscale and protein-specific evidence for the prominent, but vulnerable role of the node of Ranvier for axonal integrity. Furthermore, we show that super-resolution imaging can identify, quantify and map elongated periodic protein distances and protein interaction in histopathological tissue samples. We thus introduce a promising tool for further translational applications of super resolution microscopy.
... Caspr is highly expressed on the axon membranes of central and peripheral myelinated nerve fibers at the paranodal region, and NF155 expressed by glial cells connects the myelin sheath to the axon by binding to Caspr. Damage or dysfunction of nodes of Ranvier was reported to contribute to the pathophysiology of various neurological diseases (Susuki, 2013). However, whether orofacial mechanical hyperalgesia in TN is related to abnormal structural changes in nodes of Ranvier in the TREZ remains controversial. ...
Introduction
The aim of this study was to investigate the effect and possible mechanisms of the blood-nerve barrier (BNB) and the coagulation-anticoagulation system in modulating the mechanical allodynia in a trigeminal neuralgia (TN) rat model induced by chronic compression of the trigeminal root entry zone (TREZ).
Methods
Von Frey filaments were applied to determine the orofacial mechanical allodynia threshold. The BNB permeability was evaluated by Evans blue extravasation test. Immunohistochemical staining and laser confocal microscopy were used to measure the length of the depletion zones of the nodes of Ranvier in the TREZ, the diameter of nerve fibers and the length of the nodal gap. The transcriptional levels of prothrombin and endogenous thrombin inhibitor protease nexin-1 (PN-1) in the TREZ of TN rats were assessed by RT-qPCR. A Western blotting assay was performed to detect the expression of paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) in the TREZ. The spatiotemporal expression pattern of thrombin activated receptor (i.e. protease activated receptor 1, PAR1) in TREZ were defined by immunostaining and immunoblotting assays. PAR1 receptor inhibitors SCH79797 were administrated to TN rats to analyze the effect of thrombin-PAR1 on orofacial hyperalgesia.
Results
A compression injury of a rat’s TREZ successfully induced TN-like behavior and was accompanied by the destruction of the permeability of the BNB and the promotion of prothrombin and thrombin inhibitor protease nexin-1 (PN-1) expression. The expression of the paranodal proteins neurofascin-155 (NF155) and neurofascin-125 (NF125) was increased, while the nodal gap length of the nodes of Ranvier was widened and the length of node-depleted zones was shortened. Moreover, the expression of PAR1 within the TREZ was upregulated at an early stage of TN, and administration of the PAR1 antagonist SCH79797 effectively ameliorated orofacial mechanical allodynia.
Conclusion
A compression injury of the TREZ increased the permeability of the BNB and induced disturbances in the local coagulation-anticoagulation system, concomitant with the structural changes in the nodes of Ranvier, thrombin-PAR1 may play a critical role in modulating orofacial mechanical hyperalgesia in a TN rat model.
... Nodes of Ranvier play a critical role in nervous systems, being responsible for the generation and transmission of action potentials. Consequently, they have received much attention both from an experimental and computational perspectives (Susuki 2013;Arancibia-Carcamo and Attwell 2014;Pods et al. 2013). Arguably, the first mathematical model of the electrical activity of the node of Ranvier was derived by Hodgkin and Huxley in their ground breaking work (Hodgkin and Huxley 1952). ...
Nodes of Ranvier play critical roles in the generation and transmission of action potentials. Alterations in node properties during pathology and/or development are known to affect the speed and quality of electrical transmission. From a modelling standpoint, nodes of Ranvier are often described by systems of ordinary differential equations neglecting or greatly simplifying their geometric structure. These approaches fail to accurately describe how fine scale alteration in the node geometry or in myelin thickness in the paranode region will impact action potential generation and transmission. Here, we rely on a finite element approximation to describe the three dimensional geometry of a node of Ranvier. With this, we are able to investigate how sensitive is the electrical response to alterations in the myelin sheath and paranode geometry. We could in particular investigate irregular loss of myelin, which might be more physiologically relevant than the uniform loss often described through simpler modelling approaches.
... Dysfunctions in the nodes of Ranvier have been demonstrated to be major contributors to the pathophysiological progression of various neurological disorders. The high density of voltage-gated sodium channels (Nav) in the excitable nodal axolemma is required for the proper conduction of action potentials [75]. Neuronal damage of any nature alters the localization and expression of ion channels, thus impairing axon-glial interactions [75]. ...
... The high density of voltage-gated sodium channels (Nav) in the excitable nodal axolemma is required for the proper conduction of action potentials [75]. Neuronal damage of any nature alters the localization and expression of ion channels, thus impairing axon-glial interactions [75]. Chronic nerve compression, for instance, can damage paranodal junctions and axonal domains, which are essential for adequate conduction of action potentials along myelinated axons [76]. ...
This study investigates the role of Sygen® in diabetic peripheral neuropathy, a severe disease that affects the peripheral nervous system in diabetic individuals. This disorder often impacts the lower limbs, causing significant discomfort and, if left untreated, progresses into more serious conditions involving chronic ulcers and even amputation in many cases. Although there are management strategies available, peripheral neuropathies are difficult to treat as they often present multiple causes, especially due to metabolic dysfunction in diabetic individuals. Gangliosides, however, have long been studied and appreciated for their role in neurological diseases. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes. This product mimics the roles displayed by neurotrophins, improving neuronal function and immunomodulation by attenuating exacerbated inflammation in neurons. Furthermore, Sygen assists in axonal stabilization and keeps nodal and paranodal regions of myelin fibers organized. This maintains an adequate propagation of action potentials and restores standard peripheral nerve function. Given the multifactorial nature of this complicated disorder, medical practitioners must carefully screen the patient to avoid confusion and misdiagnosis. There are several studies analyzing the role of Sygen in neurological disorders. However, the medical literature still needs more robust investigations such as randomized clinical trials regarding the administration of this compound for diabetic peripheral neuropathies, specifically.
... Das Nodium und Juxtaparanodium wurden nicht untersucht. Sowohl bei axonalen, als auch bei demyelinisierenden Neuropathien, aber auch bei Paranodopathien kommt es zur Schädigung von Strukturen, die im Bereich des Paranodiums lokalisiert sind(Susuki, 2013). Je nach Art und Ursache der Neuropathie kommt es aber auch zur Schädigung unterschiedlicher Strukturen, die nicht immer nur am Paranodium lokalisiert sind, wie beispielsweise des Myelins am Internodium bei demyelinisierenden Neuropathien (Vgl. ...
Ranvier-Schnürringe spielen eine entscheidende Rolle bei der schnellen Weiterleitung von elektrischen Impulsen in Nervenzellen. Bei bestimmten neurologischen Erkrankungen, den Neuropathien, kann es zu Störungen in der ultrastrukturellen Organisation verschiedener Schnürring-Proteine kommen (Doppler et al., 2018, Doppler et al., 2016). Eine detailliertere Kenntnis der genauen Anordnung dieser Schnürring-Proteine und eventueller Abweichungen von dieser Anordnung im Krankheitsfall, könnte der Schlüssel zu einer vereinfachten Diagnostik von bestimmten Neuropathie- Formen sein. Ziel meiner Arbeit war es daher, die Untersuchung der ultrastrukturellen Architektur der (para-)nodalen Adhäsionsproteine Neurofascin-155 und Caspr1 unter Verwendung der super-hochauflösenden Mikroskopiemethode dSTORM (direct Stochastic Optical Reconstruction Microscopy) an murinen Zupfnervenpräparaten zu etablieren. Nach erster Optimierung der Probenpräparation für die 2-Farben-dSTORM sowie der korrelationsbasierten Bildanalyse, konnte ich mittels modellbasierter Simulation die zugrundeliegende Molekülorganisation identifizieren und mit Hilfe der Ergebnisse aus früheren Untersuchungen validieren. In einem translationalen Ansatz habe ich anschließend humane Zupfnervenpräparate von 14 Probanden mit unterschiedlichen Formen einer Neuropathie mikroskopiert und ausgewertet, um die Anwendbarkeit dieses Ansatzes in der Diagnostik zu testen. Obgleich keine signifikanten Unterschiede zwischen physiologischem und pathologischem neurologischem Gewebe hinsichtlich Neurofascin-155 und Caspr1 festgestellt werden konnten, scheint der Ansatz grundsätzlich dennoch vielversprechend zu sein, bedarf jedoch noch weiteren Anstrengungen hinsichtlich Probenpräparation, Auswertungs- und Versuchsprotokollen und einer größeren Anzahl an humanen Biopsien mit homogenerem Krankheitsbild.
... Mikrovilli der Schwann-Zellen ausgefüllt und Neurofascin-186 bindet an NrCAM (Neuronales Zelladhäsionsmolekül) auf der Oberfläche der Schwannzellen und an von den Schwannzellen sezerniertes Gliomedin (Eshed et al., 2005;Susuki, 2013;Vural et al., 2018). ...
Die (Para-)nodopathie ist neben der primär axonalen und der primär demyelinisierenden Polyneuropathie eine neue Krankheitsentität, die sich durch eine Schädigung der Funktion des Ranvierschen Schnürringes auszeichnet. Die Forschung zu (para-)nodalen Autoantikörpern fokussierte sich bislang hauptsächlich auf Neurofascin-155- und Contactin-1-Autoantikörper der Subklasse IgG4. In dieser Studie wurden die Seren von insgesamt 264 PatientInnen mit CIDP, GBS oder anderen Formen von Polyneuropathien mittels Bindungsassays an murinen Ischiadicuszupfnerven und gegebenenfalls ELISA auf (para-)nodale Autoantikörper gescrennt. Positive Autoantikörperbefunde wurden bei IgG-Autoantikörpern mittels Bindungsassays an transfizierten HEK-293-Zellen und bei IgM-Autoantikörpern mittels Western Blot bestätigt. ELISA Untersuchungen dienten zur näheren Spezifizierung. Weiterhin wurde die zeitabhängige Wirkung von Contactin-1-Autoantikörpern im Zellkulturmodell untersucht. Die im folgenden dargestellten Ergebnisse zeigen, dass die (Para-)nodopathie nicht auf die bisher am häufigsten beschriebene Erkrankung mit IgG4-Autoantikörpern beschränkt werden sollte. Bei dem extrem schwer betroffenen IgG-Patient 1 konnte ein Pan-Neurofascin-IgG3-Autoantikörper nachgewiesen werden. Als charakteristische Symptome für diese Autoantikörper konnten in Übereinstimmung mit weiteren Fallberichten Tetraplegie, Beatmungspflichtigkeit sowie eine schwere Hirnnervenbeteiligung bis zur Locked-In-Symptomatik identifiziert werden. Diese Patienten heben sich deutlich von den PatientInnen mit den bisher hauptsächlich beschriebenen Neurofascin-155-IgG4-Autoantikörpern ab, die wie IgG-Patient 2 charakteristischerweise in jungem Alter an einer CIDP mit Tremor ohne Besserung unter IVIG-Therapie leiden. Es wurden fünf PatientInnen mit Neurofascin-155-IgM-Autoantikörpern identifiziert, die eine akut beginnende Erkrankung mit Tetraparese, Tremor und neuropathischen Schmerzen zeigten. Ob sich dieser Phänotyp als charakteristisch für eine Neurofascin-155-IgM-(Para-)nodopathie bestätigt, sollte in weiteren Studien untersucht werden. Im murinen Zellkulturmodell an cerebellären Neuronen und Spinalganglienneuronen zeigte sich nach Inkubation mit Contactin-1-IgG-Patientenantikörpern eine zeitabhängige, rasch reversible Verminderung der Contactin-1-Protein-Expression in immunhistochemischen Färbungen sowie Western Blots, die durch eine Internalisierung des Contactin-1-Proteins erklärbar wäre. Der Angriff von Autoantikörpern an Spinalganglienneuronen und cerebellären Neurone sollte in weitere pathophysiologische Überlegungen miteinbezogen werden, da hierdurch typische Symptome der (Para-)nodopathie wie eine sensible Ataxie oder ein cerebellärer Tremor erklärt werden könnten.
... Abnormal development or disruption of the nodal and paranodal microdomains contributes to a wide range of neurological diseases (Susuki, 2013). While there is abundant information about molecular microdomains in the node of Ranvier in other nervous systems (Crawford et al., 2009;Devaux & Scherer, 2005), the study of node microdomains in the peripheral auditory system is very limited. ...
... Loss/dysfunction of nodal components and demyelination have been associated with neurological symptoms of aging (Hinman et al., 2006) and diseases such as Guillain-Barré syndrome and multiple sclerosis (Susuki, 2013). The relationship between aging and changes in nodal structures of the AN has yet to be elucidated. ...
The auditory nerve (AN) of the inner ear is the primary conveyor of acoustic information from sensory hair cells to the brainstem. Approximately 95% of peripheral AN fibers are myelinated by glial cells. The integrity of myelin and the glial-associated paranodal structures at the node of Ranvier is critical for normal AN activity and axonal survival and function in the central auditory nervous system. However, little is known about the node of Ranvier's spatiotemporal development in the AN, how the aging process (or injury) affects the activity of myelinating glial cells, and how downstream alterations in myelin and paranodal structure contribute to AN degeneration and sensorineural hearing loss. Here, we characterized two types of Ranvier nodes—the axonal node and the ganglion node—in the mouse peripheral AN, and found that they are distinct in several features of postnatal myelination and age-related degeneration. Cellular, molecular, and structure–function correlations revealed that the two node types are each critical for different aspects of peripheral AN function. Neural processing speed and synchrony is associated with the length of the axonal node, while stimulus level-dependent amplitude growth and action potentials are associated with the ganglion node. Moreover, our data indicate that dysregulation of glial cells (e.g., satellite cells) and degeneration of the ganglion node structure are an important new mechanism of age-related hearing loss.
... Such a dynamic balance is maintained by the interaction of glial cells with ion channels, other membrane proteins and the cytoskeleton 46 . Impairment of this complex is often associated to the development of neurodegenerative diseases, such as multiple sclerosis 47 . Therefore, further studies on the possible role of photons in the regulatory mechanisms of node-myelin functional unit may provide a better knowledge and new therapeutic options for neurodegenerative diseases. ...
The nervous system is one of the most complex expressions of biological evolution. Its high performance mostly relies on the basic principle of the action potential, a sequential activation of local ionic currents along the neural fiber. The implications of this essentially electrical phenomenon subsequently emerged in a more comprehensive electromagnetic perspective of neurotransmission. Several studies focused on the possible role of photons in neural communication and provided evidence of the transfer of photons through myelinated axons. A hypothesis is that myelin sheath would behave as an optical waveguide, although the source of photons is controversial. In a previous work, we proposed a model describing how photons would arise at the node of Ranvier. In this study we experimentally detected photons in the node of Ranvier by Ag ⁺ photoreduction measurement technique, during electrically induced nerve activity. Our results suggest that in association to the action potential a photonic radiation takes place in the node.
