Review

Authors: Menachem Hanani, David C Spray

Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic protein, stronger gap junction-mediated SGC-SGC and neuron-SGC coupling, increased sensitivity to ATP, downregulation of Kir4.1 potassium channels and increased cytokine synthesis and release. There is evidence that these changes in SGCs contribute to chronic pain by augmenting neuronal activity and that these changes are consistent in various rodent pain models and likely also in human pain. Therefore, understanding these changes and the resulting abnormal interactions of SGCs with sensory neurons could provide a mechanistic approach that might be exploited therapeutically in alleviation and prevention of pain. We describe how SGCs are altered in rodent models of four common types of pain: systemic inflammation (sickness behaviour), post-surgical pain, diabetic neuropathic pain and post-herpetic pain.

Topics: Animals; Chronic Pain; Ganglia, Autonomic; Ganglia, Sensory; Humans; Satellite Cells, Perineuronal

PubMed: 32699292
DOI: 10.1038/s41583-020-0333-z

Authors: Aurelia A Mapps, Michael B Thomsen, Erica Boehm...

Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.

Topics: Animals; Ganglia, Sensory; Ganglia, Spinal; Ganglia, Sympathetic; Humans; Mice; Neuroglia; Neurons; Neurons, Afferent; Peripheral Nervous System; Schwann Cells

PubMed: 35108545
DOI: 10.1016/j.celrep.2022.110328

Authors: Joel Gutierrez, Jose-Alberto Palma, Horacio Kaufmann...

Acute-onset and severe sensory and autonomic deficits with no motor dysfunction, typically preceded by a febrile illness, with poor recovery, and often fatal outcome are the hallmark features of acute sensory and autonomic neuronopathy (ASANN). Pathologically and electrophysiologically, ASANN is characterized by an extensive ganglionopathy affecting sensory and autonomic ganglia with preservation of motor neurons. Consequently, patients, usually children or young adult, develop acute-onset profound widespread loss of all sensory modalities resulting in automutilations, as well as autonomic failure causing neurogenic orthostatic hypotension, neurogenic underactive bladder, and gastroparesis and constipation. The diagnosis is clinical with support of nerve conduction studies and autonomic testing, as well as spinal cord magnetic resonance imaging showing characteristic posterior cord hyperintensities. Although the presumed etiology is immune-mediated, further studies are required to clarify the physiopathology of the disease. We here performed a systematic review of the epidemiology, pathophysiology, diagnosis, and management of ASANN, with three representative cases that recently presented at our clinic. All three patients had the typical clinical manifestations of ASANN but in different combinations, illustrating the variable phenotype of the disorder. Immunosuppression is seldom effective. Management options are limited to supportive and symptomatic care with the goal of minimizing complications and preventing death.

Topics: Autonomic Nervous System Diseases; Ganglia, Autonomic; Ganglia, Sensory; Humans

PubMed: 32906171
DOI: 10.1055/s-0040-1713843

Authors: Eman Qarot, Yun Guan, Menachem Hanani...

Neurons in sensory ganglia are wrapped completely by satellite glial cells (SGCs). One putative function of SGCs is to regulate the neuronal microenvironment, but this role has received only little attention. In this study we investigated whether the SGC envelope serves a barrier function and how SGCs may control the neuronal microenvironment. We studied this question on short-term (<24 h) cell cultures of dorsal root ganglia and trigeminal ganglia from adult mice, which contain neurons surrounded with SGCs, and neurons that are not. Using calcium imaging, we measured neuronal responses to molecules with established actions on sensory neurons. We found that neurons surrounded by SGCs had a smaller response to molecules such as adenosine triphosphate (ATP), glutamate, GABA, and bradykinin than neurons without glial cover. When we inhibited the activity of NTPDases, which hydrolyze the ATP, and also when we inhibited the glutamate and GABA transporters on SGCs, this difference in the neuronal response was no longer observed. We conclude that the SGC envelope does not hinder diffusional passage, but acts as a metabolic barrier that regulates the neuronal microenvironment, and can protect the neurons and modulate their activity.

Topics: Animals; Mice; Neuroglia; Neurons; Ganglia, Sensory; Ganglia, Spinal; Glutamates; Adenosine Triphosphate; Satellite Cells, Perineuronal

PubMed: 38450799
DOI: 10.1002/glia.24511

Review

Authors: Uwe Ernsberger

Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.

Topics: Animals; Cell Differentiation; Ganglia, Spinal; Ganglia, Sympathetic; Nerve Growth Factors; Neurons; Signal Transduction

PubMed: 19387688
DOI: 10.1007/s00441-009-0784-z

Review

Authors: Isabel Espinosa-Medina, Orthis Saha, Franck Boismoreau...

We recently defined genetic traits that distinguish sympathetic from parasympathetic neurons, both preganglionic and ganglionic (Espinosa-Medina et al., Science 354:893-897, 2016). By this set of criteria, we found that the sacral autonomic outflow is sympathetic, not parasympathetic as has been thought for more than a century. Proposing such a belated shift in perspective begs the question why the new criterion (cell types defined by their genetic make-up and dependencies) should be favored over the anatomical, physiological and pharmacological considerations of long ago that inspired the "parasympathetic" classification. After a brief reminder of the former, we expound the weaknesses of the latter and argue that the novel genetic definition helps integrating neglected anatomical and physiological observations and clearing the path for future research.

Topics: Ganglia, Parasympathetic; Ganglia, Sympathetic; Humans; Sacrococcygeal Region; Spinal Cord

PubMed: 29103139
DOI: 10.1007/s10286-017-0478-7

Authors: Anna C Schneider, David Fox, Omar Itani...

In oscillatory circuits, some actions of neuromodulators depend on the oscillation frequency. However, the mechanisms are poorly understood. We explored this problem by characterizing neuromodulation of the lateral pyloric (LP) neuron of the crab stomatogastric ganglion (STG). Many peptide modulators, including proctolin, activate the same ionic current () in STG neurons. Because is fast and non-inactivating, its peak level does not depend on the temporal properties of neuronal activity. We found, however, that the amplitude and peak time of the proctolin-activated current in LP is frequency dependent. Because frequency affects the rate of voltage change, we measured these currents with voltage ramps of different slopes and found that proctolin activated two kinetically distinct ionic currents: the known , whose amplitude is independent of ramp slope or direction, and an inactivating current (), which was only activated by positive ramps and whose amplitude increased with increasing ramp slope. Using a conductance-based model we found that and make distinct contributions to the bursting activity, with increasing the excitability, and regulating the burst onset by modifying the postinhibitory rebound in a frequency-dependent manner. The voltage dependence and partial calcium permeability of is similar to other characterized neuromodulator-activated currents in this system, suggesting that these are isoforms of the same channel. Our computational model suggests that calcium permeability may allow this current to also activate the large calcium-dependent potassium current in LP, providing an additional mechanism to regulate burst termination. These results demonstrate a mechanism for frequency-dependent actions of neuromodulators.

Topics: Action Potentials; Animals; Brachyura; Ganglia; Ganglia, Invertebrate; Neurons; Neurotransmitter Agents; Pylorus

PubMed: 34593519
DOI: 10.1523/ENEURO.0338-21.2021

Authors: Laura Taberner, Aitor Bañón, Berta Alsina...

There is growing evidence of a direct influence of vasculature on the development of neurons in the brain. The development of the cranial vasculature has been well described in zebrafish but its anatomical relationship with the adjacent developing sensory ganglia has not been addressed. Here, by 3D imaging of fluorescently labelled blood vessels and sensory ganglia, we describe for the first time the spatial organization of the cranial vasculature in relation to the cranial ganglia during zebrafish development. We show that from 24 h post-fertilization (hpf) onwards, the statoacoustic ganglion (SAG) develops in direct contact with two main blood vessels, the primordial hindbrain channel and the lateral dorsal aortae (LDA). At 48 hpf, the LDA is displaced medially, losing direct contact with the SAG. The relationship of the other cranial ganglia with the vasculature is evident for the medial lateral line ganglion and for the vagal ganglia that grow along the primary head sinus (PHS). We also observed that the innervation of the anterior macula runs over the PHS vessel. Our spatiotemporal anatomical map of the cranial ganglia and the head vasculature indicates physical interactions between both systems and suggests a possible functional interaction during development.

Topics: Animals; Blood Vessels; Brain; Cranial Nerves; Ganglia; Zebrafish

PubMed: 29235648
DOI: 10.1111/joa.12762

Authors: Kwang Ho Cho, Ji Hyun Kim, Zhe Wu Jin...

Although pulmonary ganglia were considered to be an analogue of the myenteric ganglia of intestines in embryos, there seemed to be no morphological evaluation in the later stage of development. We conducted immunostainings of intrapulmonary nerves using 17 human fetuses at 14-18 and 28-34 weeks. The ganglion cells were small (15-20 μm in diameter) in the earlier group, but they increased in size (20-30 μm) in the late group. One ganglion, containing 5-30 cell bodies, was usually located "outside" of the bronchial smooth muscle or cartilage. In addition, a few ganglion was found beneath the mucosa of the trachea and principal bronchi. The highest density of ganglia (5-15 ganglia per section with 50 μm interval) was found at the origin of the subsegmental bronchi, but ganglia were absent along more peripheral bronchi those are responsible for contraction and obstruction of the airway. Therefore, in topographical relation between smooth muscle and nerve, intrapulmonary intrinsic neurons were different from intestinal myenteric neurons. Consequently, a previous hypothesis of "embryonic intramuscular bronchial ganglia" seemed not to be based on observations of the peripheral bronchus but on the central bronchus than the sub-subsegmental level. An extrinsic migration and redistribution of ganglia might occur at midterm to provide the final location outside of airway smooth muscles. Finally, no ganglion cell bodies were positive either for neuronal nitric oxide synthase or tyrosine hydroxylase. Instead of the classical entity of autonomic nerves, nonadrenergic noncholinergic (NANC) innervation might be dominant even in fetuses. Anat Rec, 302:2233-2244, 2019. © 2019 American Association for Anatomy.

Topics: Bronchi; Fetus; Ganglia; Humans; Intestines; Muscle, Smooth; Neurons

PubMed: 31241243
DOI: 10.1002/ar.24208

Authors: Hermanas Inokaitis, Neringa Pauziene, Dainius H Pauza...

The sinoatrial node (SAN) has been the object of interest of various studies. In experimental neurocardiology, the real challenge is the choice of the most appropriate animal model. Pig is routinely used animal due to its size and physiological features. Despite this, the anatomy and innervation of the pig SAN are not completely examined. This study analyses the distribution of SAN cells and their innervation in whole-mount preparations and the cross-sections of the pig right atrium. Our findings revealed the differences in the distribution of the SAN cells and their innervation pattern between pigs and other animals. The pig SAN myocytes were distributed around the root of the anterior vena cava. A meshwork of nerve fibers (NFs) in this area was four-fold denser compared to other right atrial areas and contained the adrenergic (positive for TH), cholinergic (positive for ChAT), nitrergic (positive for nNOS), and potentially sensory (positive for SP) NFs. The SAN area contained 98 ± 10 ganglia that involved 21 ± 2 neuronal somata per ganglion. The determined chemical phenotypes of ganglionic cells demonstrate their diversity in the pig SAN area as there were identified neuronal somata positive for ChAT, nNOS, TH, and simultaneously for ChAT/nNOS and ChAT/TH. Small intensively fluorescent cells were also abundant. The broad distribution of SAN cells, the chemical diversity, and the high density of neural components in the SAN area are comparable to the human one and, therefore, the pig may be considered as the appropriate animal model for experimental cardiology.

Topics: Humans; Animals; Swine; Sinoatrial Node; Nervous System; Neurons; Nerve Fibers; Ganglia

PubMed: 35643929
DOI: 10.1002/ar.24998