Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo

Goldstein, Robert H.; Barkai, Omer; Íñigo-Portugués, Almudena; Katz, Ben; Lev, Shaya; Binshtok, Alexander M.

doi:10.1016/j.neuron.2019.03.005

Cited by 31 publications

(89 citation statements)

References 53 publications

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“…Instead, electrophysiological studies have shown that the SIZ of DRGs is located in the peripheral axon, slightly removed from the dendritic compartment ( Fig. 1 A, ii); similar to the AIS, this peripheral SIZ is dynamic and moves closer to the dendrites upon sensitization (Goldstein et al, 2019). Whether it displays AnkG expression and/or an electron-dense undercoat remains to be seen.…”

Section: Do Ais Features Apply To Other Neuron Classes?mentioning

confidence: 96%

Cytoskeletal organization of axons in vertebrates and invertebrates

Prokop

2020

Journal of Cell Biology

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The maintenance of axons for the lifetime of an organism requires an axonal cytoskeleton that is robust but also flexible to adapt to mechanical challenges and to support plastic changes of axon morphology. Furthermore, cytoskeletal organization has to adapt to axons of dramatically different dimensions, and to their compartment-specific requirements in the axon initial segment, in the axon shaft, at synapses or in growth cones. To understand how the cytoskeleton caters to these different demands, this review summarizes five decades of electron microscopic studies. It focuses on the organization of microtubules and neurofilaments in axon shafts in both vertebrate and invertebrate neurons, as well as the axon initial segments of vertebrate motor- and interneurons. Findings from these ultrastructural studies are being interpreted here on the basis of our contemporary molecular understanding. They strongly suggest that axon architecture in animals as diverse as arthropods and vertebrates is dependent on loosely cross-linked bundles of microtubules running all along axons, with only minor roles played by neurofilaments.

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Section: Do Ais Features Apply To Other Neuron Classes?mentioning

confidence: 96%

Cytoskeletal organization of axons in vertebrates and invertebrates

Prokop

2020

Journal of Cell Biology

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“…Navs (Goldstein et al, 2019). The length of the terminal and the passive part of the terminal branch is similar among different terminals (Goldstein et al, 2019); thus, the length of the conductive part defines the overall length of the terminal branch. The terminal branches converging onto the fibers constructing the nociceptive terminal tree (Belmonte et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…The model neuron of all tree structures includes the following Hodgkin-Huxley-type ion channels used in Barkai et al (Barkai et al, 2017) and Goldstein et al (Goldstein et al, 2019):…”

Section: Active Conductancesmentioning

confidence: 99%

“…A capsaicin-like induced current was introduced into a single simplified voltage-clamp point-process with fast exponential activation and slow exponential inactivation mimicking the experimental kinetics of puff-applied 1 μM capsaicin-induced current and sufficient to induce action potential firing when applied onto the acutely dissociated dorsal root ganglion neuron (Nita et al, 2016). The similar current was used in Barkai et al (Barkai et al, 2017) and Goldstein et al (Goldstein et al, 2019) to generate activity in the modeled nociceptive neuron when applied to the single 75 m length terminal:…”

Section: Stimulation Parametersmentioning

confidence: 99%

“…The biophysical properties and spatial distribution of functional transducer and voltage-gated channels expressed by nociceptive neurons are essential factors in defining the gain of the terminals, i.e., the number and pattern of action potential firing resulting from activation of the terminal by noxious stimuli (Dib-Hajj et al, 2010;Waxman and Zamponi, 2014;Goldstein et al, 2019). The current electrophysiological and imaging approaches allow studying how a single terminal encodes the information (Vasylyev and Waxman, 2012;Goldstein et al, 2019). Skinnerve (Reeh, 1986) or teased preparations (Tal and Devor, 1992) permit studying how the whole nociceptive terminal trees respond to stimulation.…”

Section: Introductionmentioning

confidence: 99%

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The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals

Barkai

Butterman

Katz

et al. 2020

Preprint

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The output from the peripheral terminals of primary nociceptive neurons, which detect and encode the information regarding noxious stimuli, is crucial in determining pain sensation. The nociceptive terminal endings are morphologically complex structures assembled from multiple branches of different geometry, which converge in a variety of forms to create the terminal tree. The output of a single terminal is defined by the properties of the transducer channels producing the generation potentials and voltage-gated channels, translating the generation potentials into action potential firing. However, in the majority of cases, noxious stimuli activate multiple terminals; thus, the output of the nociceptive neuron is defined by the integration and computation of the inputs of the individual terminals. Here we used a computational model of nociceptive terminal tree to study how the architecture of the terminal tree affects input-output relation of the primary nociceptive neurons. We show that the input-output properties of the nociceptive neurons depend on the length, the axial resistance, and location of individual terminals. Moreover, we show that activation of multiple terminals by capsaicin-like current allows summation of the responses from individual terminals, thus leading to increased nociceptive output. Stimulation of terminals in simulated models of inflammatory or nociceptive hyperexcitability led to a change in the temporal pattern of action potential firing, emphasizing the role of temporal code in conveying key information about changes in nociceptive output in pathological conditions, leading to pain hypersensitivity.Significance statementNoxious stimuli are detected by terminal endings of the primary nociceptive neurons, which are organized into morphologically complex terminal trees. The information from multiple terminals is integrated along the terminal tree, computing the neuronal output, which propagates towards the CNS, thus shaping the pain sensation. Here we revealed that the structure of the nociceptive terminal tree determines the output of the nociceptive neurons. We show that the integration of noxious information depends on the morphology of the terminal trees and how this integration and, consequently, the neuronal output change under pathological conditions. Our findings help to predict how nociceptive neurons encode noxious stimuli and how this encoding changes in pathological conditions, leading to pain.

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Neurophysiology of corneal neuropathic pain and emerging pharmacotherapeutics

Asiedu

2023

J of Neuroscience Research

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The altered activity generated by corneal neuronal injury can result in morphological and physiological changes in the architecture of synaptic connections in the nervous system. These changes can alter the sensitivity of neurons (both second‐order and higher‐order projection) projecting pain signals. A complex process involving different cell types, molecules, nerves, dendritic cells, neurokines, neuropeptides, and axon guidance molecules causes a high level of sensory rearrangement, which is germane to all the phases in the pathomechanism of corneal neuropathic pain. Immune cells migrating to the region of nerve injury assist in pain generation by secreting neurokines that ensure nerve depolarization. Furthermore, excitability in the central pain pathway is perpetuated by local activation of microglia in the trigeminal ganglion and alterations of the descending inhibitory modulation for corneal pain arriving from central nervous system. Corneal neuropathic pain may be facilitated by dysfunctional structures in the central somatosensory nervous system due to a lesion, altered synaptogenesis, or genetic abnormality. Understanding these important pathways will provide novel therapeutic insight.

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Location and Plasticity of the Sodium Spike Initiation Zone in Nociceptive Terminals In Vivo

Cited by 31 publications

References 53 publications

Cytoskeletal organization of axons in vertebrates and invertebrates

Cytoskeletal organization of axons in vertebrates and invertebrates

The input-output relation of primary nociceptive neurons is determined by the morphology of the peripheral nociceptive terminals

Neurophysiology of corneal neuropathic pain and emerging pharmacotherapeutics

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