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Progress in Brain Research 2006Spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia that is often triggered by... (Review)
Review
Spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia that is often triggered by distension of pelvic viscera (bladder or bowel). This syndrome is characterized by episodic hypertension due to sudden, massive discharge of sympathetic preganglionic neurons in the thoracolumbar spinal cord. This hypertension is usually accompanied by bradycardia, particularly if the injury is caudal to the 2nd to 4th thoracic spinal segments. The development of autonomic dysreflexia is correlated with aberrant sprouting of peptidergic afferent fibers into the spinal cord below the injury. In particular, sprouting of nerve growth factor-responsive afferent fibers has been shown to have a major influence on dysreflexia, perhaps by amplifying the activation of disinhibited sympathetic neurons. Using a model of noxious bowel distension after complete thoracic spinal transection at the 4th thoracic segment in rats, we selectively altered C-fiber sprouting, at specified spinal levels caudal to the injury, with microinjections of adenovirus encoding the growth-promoting nerve growth factor or the growth-inhibitory semaphorin 3A. This was followed by assessment of physiological responses to colorectal distension and subsequent histology. Additionally, anterograde tract tracers were injected into the lumbosacral region to compare the extent of labeled propriospinal rostral projections in uninjured cords to those in cords after complete 4th thoracic transection. In summary, overexpression of chemorepulsive semaphorin 3A impeded C-fiber sprouting in lumbosacral segments and mitigated hypertensive autonomic dysreflexia, whereas the opposite results were obtained with nerve growth factor overexpression. Furthermore, compared to naïve rats, there were significantly more labeled lumbosacral propriospinal projections rostrally after thoracic injury. Collectively, our findings suggest that distension of pelvic viscera increases the excitation of expanded afferent terminals in the disinhibited lumbosacral spinal cord. This, in turn, triggers excitation and sprouting of local propriospinal neurons to relay visceral sensory stimuli and amplify the activation of sympathetic preganglionic neurons in the thoracolumbar cord, to enhance transmission in the spinal viscero-sympathetic reflex pathway. These responses are manifested as autonomic dysreflexia.
Topics: Adrenergic Fibers; Animals; Autonomic Dysreflexia; Autonomic Fibers, Preganglionic; Calcitonin Gene-Related Peptide; Humans; Hypertension; Nerve Growth Factor; Neurons; Reflex; Spinal Cord; Spinal Cord Injuries; Thoracic Vertebrae; Viscera
PubMed: 16198706
DOI: 10.1016/S0079-6123(05)52017-X -
Journal of Integrative Neuroscience Sep 2021Location and distribution of spinal sympathetic preganglionic neurons projecting to the superior cervical ganglion were investigated in a rodent model organism for...
Location and distribution of spinal sympathetic preganglionic neurons projecting to the superior cervical ganglion were investigated in a rodent model organism for photoperiodic regulation, the Djungarian hamster (). Upon unilateral injection of Fluoro-Gold into the superior cervical ganglia, retrograde neuronal tracing demonstrated labeled neurons ipsilateral to the injection site. They were seen in spinal segments C8 to Th5 of which the segments Th1 to Th3 contained about 98% of the labeled cells. Neurons were found in the spinal cord predominantly in the intermediolateral nucleus pars principalis and pars funicularis. At the same time, the central autonomic area and the intercalated region contained only very few labeled cells. In the intermediolateral nucleus, cells often were arranged in clusters, of which several were seen in each spinal segment. Selected sections were exposed to antibodies directed against arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or substance P. It was found that about two-thirds of sympathetic preganglionic neurons produced the gaseous neuroactive substance nitric oxide and that few contained small amounts of neuropeptide Y. Fibers of putative supraspinal origin immunopositive for either arginine-vasopressin, neuronal nitric oxide synthase, neuropeptide Y, neurotensin, oxytocin or, in particular, substance P were found in the vicinity of labeled sympathetic preganglionic neurons. These results demonstrate the location of relay neurons for autonomic control of cranial and cardial structures and provide further knowledge on neurochemical properties of sympathetic preganglionic neurons and related structures.
Topics: Animals; Autonomic Pathways; Cricetinae; Interneurons; Male; Neuroanatomical Tract-Tracing Techniques; Photoperiod; Spinal Cord
PubMed: 34645089
DOI: 10.31083/j.jin2003060 -
Autonomic Neuroscience : Basic &... Sep 2020Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These... (Review)
Review
BACKGROUND
Cardiac sympathetic blockade is a therapeutic approach for arrhythmias and heart failure and may be a beneficial effect of high thoracic epidural anesthesia. These treatments require detailed knowledge of the spatial location and distribution of cardiac autonomic nerves, however, there are controversies on this subject in humans.
OBJECTIVE
To provide a systematic overview of current knowledge on human anatomy of the cardiac autonomic nervous system.
RESULTS
In contrast to the often claimed assumption that human preganglionic sympathetic cardiac neurons originate mainly from thoracic spinal segments T1-T4 or T5, there is ample evidence indicating involvement of cervical spinal segment C8 and thoracic spinal segments below T5. Whether cervical ganglia besides the stellate ganglion play a role in transmission of cardiac sympathetic signals is unclear. Similarly, there is debate on the origin of cardiac nerves from different thoracic ganglia. Most human studies report thoracic cardiac nerves emerging from the first to fourth thoracic paravertebral ganglia; others report contributions from the fifth, sixth and even the seventh thoracic ganglia. There is no agreement on the precise composition of nerve plexuses at the cardiac level. After years of debate, it is generally accepted that the vagal nerve contributes to ventricular innervation. Vagal distribution appears higher in atria, whereas adrenergic fibers exceed the number of vagal fibers in the ventricles.
CONCLUSION
Anatomy of the human cardiac autonomic nervous system is highly variable and likely extends beyond generally assumed boundaries. This information is relevant for thoracic epidural anesthesia and procedures targeting neuronal modulation of cardiac sympathetic innervation.
Topics: Adult; Animals; Autonomic Nervous System; Ganglia, Sympathetic; Heart; Humans
PubMed: 32497872
DOI: 10.1016/j.autneu.2020.102674 -
Japanese Journal of Pharmacology Jan 2002Maintenance of blood pressure is mostly dependent on sympathetic "tone", and the sympathetic nerve innervates the entire vascular bed, excepting the capillaries.... (Review)
Review
Maintenance of blood pressure is mostly dependent on sympathetic "tone", and the sympathetic nerve innervates the entire vascular bed, excepting the capillaries. Although norepinephrine (NE) is the principal neurotransmitter released upon sympathetic nerve stimulation, neuropeptide Y and ATP are cotransmitters in various vascular tissues. In addition, dopamine and epinephrine, as well as acetylcholine, have been shown to be sympathetic neurotransmitters in specific vasculatures. Transmitter NE release is modified by a number of endogenous substances including the transmitter itself. Chronic denervation of the preganglionic fiber induces an increase in NE release per pulse, indicating postganglionic neuronal supersensitivity. So far, three main adrenoceptor types have been shown, alpha1, alpha2 and beta, each of which is further divided into at least three subtypes, as well as the alpha1L-adrenoceptor, a phenotype of the cloned alpha1a-adrenoceptor, in the blood vessel. Thus, the response of vessels with different receptor types to a transmitter varies quantitatively and even qualitatively from one vessel to another. The remarkable diversity in the sympathetic innervation mechanism in the vascular system may play an important role in regional variations in the regulation of blood flow. The sympathetic nerve also exerts long-term trophic action on the blood vessel. In conclusion, the sympathetic nervous system plays an important role not only in the regulation of cardiovascular dynamics but in the maintenance of the vessel structure, as well.
Topics: Animals; Cardiovascular System; Humans; Neurotransmitter Agents; Receptors, Adrenergic; Regional Blood Flow; Sympathomimetics; Vasomotor System
PubMed: 11855682
DOI: 10.1254/jjp.88.9 -
The Journal of Comparative Neurology Feb 2014There are two muscle fiber types in extraocular muscles: those receiving a single motor endplate, termed singly innervated fibers (SIFs), and those receiving multiple...
There are two muscle fiber types in extraocular muscles: those receiving a single motor endplate, termed singly innervated fibers (SIFs), and those receiving multiple small terminals along their length, termed multiply innervated fibers (MIFs). In monkeys, these two fiber types receive input from different motoneuron pools: SIF motoneurons found within the extraocular motor nuclei, and MIF motoneurons found along their periphery. For the monkey medial rectus muscle, MIF motoneurons are found in the C-group, while SIF motoneurons lie in the A- and B-groups. We analyzed the somatodendritic morphology and ultrastructure of these three subgroups of macaque medial rectus motoneurons to better understand the structural determinants controlling the two muscle fiber types. The dendrites of A- and B-group motoneurons lay within the oculomotor nucleus, but those of the C-group motoneurons were located outside the nucleus, and extended into the preganglionic Edinger-Westphal nucleus. A- and B-group motoneurons were very similar ultrastructurally. In contrast, C-group motoneurons displayed significantly fewer synaptic contacts on their somata and proximal dendrites, and those contacts were smaller in size and lacked dense-cored vesicles. However, the synaptic structure of C-group distal dendrites was quite similar to that observed for A- and B-group motoneurons. Our anatomical findings suggest that C-group MIF motoneurons have different physiological properties than A- and B-group SIF motoneurons, paralleling their different muscle fiber targets. Moreover, primate C-group motoneurons have evolved a special relationship with the preganglionic Edinger-Westphal nucleus, suggesting these motoneurons play an important role in near triad convergence to support increased near work requirements.
Topics: Animals; Electron Microscope Tomography; Macaca fascicularis; Male; Motor Neurons; Oculomotor Muscles; Presynaptic Terminals; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
PubMed: 23897455
DOI: 10.1002/cne.23437 -
Nature Communications Sep 2015The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside...
The sympathetic nervous system is essential for maintaining mammalian homeostasis. How this intricately connected network, composed of preganglionic neurons that reside in the spinal cord and post-ganglionic neurons that comprise a chain of vertebral sympathetic ganglia, arises developmentally is incompletely understood. This problem is especially complex given the vertebral chain of sympathetic ganglia derive secondarily from the dorsal migration of 'primary' sympathetic ganglia that are initially located several hundred microns ventrally from their future pre-synaptic partners. Here we report that the dorsal migration of discrete ganglia is not a simple migration of individual cells but a much more carefully choreographed process that is mediated by extensive interactions of pre-and post-ganglionic neurons. Dorsal migration does not occur in the absence of contact with preganglionic axons, and this is mediated by BDNF/TrkB signalling. Thus BDNF released by preganglionic axons acts chemotactically on TrkB-positive sympathetic neurons, to pattern the developing peripheral nervous system.
Topics: Animals; Autonomic Fibers, Preganglionic; Axons; Brain-Derived Neurotrophic Factor; Cell Movement; Chemotaxis; Chick Embryo; Ganglia, Sympathetic; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; In Vitro Techniques; Microscopy, Confocal; Receptor, trkB; Signal Transduction; Spinal Cord; Sympathetic Nervous System; Time-Lapse Imaging
PubMed: 26404565
DOI: 10.1038/ncomms9281 -
The Journal of Physiology Jul 2019Spinally-projecting neurons of the rostral ventrolateral medulla (RVLM) determine sympathetic outflow to different territories of the body. Previous studies suggest the...
KEY POINTS
Spinally-projecting neurons of the rostral ventrolateral medulla (RVLM) determine sympathetic outflow to different territories of the body. Previous studies suggest the existence of RVLM neurons with distinct functional classes, such as neurons that target sympathetic nerves bound for functionally-similar tissue types (e.g. muscle vasculature). The existence of RVLM neurons with more general actions had not been critically tested. Using viral tracing, we show that a significant minority of RVLM neurons send axon collaterals to disparate spinal segments (T and T ). Furthermore, optogenetic activation of sympathetic premotor neurons projecting to lumbar spinal segments also produced activation of sympathetic nerves from rostral spinal segments that innervate functionally diverse tissues (heart and forelimb muscle). These findings suggest the existence of individual RVLM neurons for which the axons branch to drive sympathetic preganglionic neurons of more than one functional class and may be able to produce global changes in sympathetic activity.
ABSTRACT
We investigate the extent of spinal axon collateralization of rat rostral ventrolateral medulla (RVLM) sympathetic premotor neurons and its functional consequences. In anatomical tracing experiments, two recombinant herpes viral vectors with retrograde tropism and expressing different fluorophores were injected into the intermediolateral column at upper thoracic and lower thoracic levels. Histological analysis revealed that ∼21% of RVLM bulbospinal neurons were retrogradely labelled by both vectors, indicating substantial axonal collateralization to disparate spinal segments. In functional experiments, another virus with retrograde tropism, a canine adenovirus expressing Cre recombinase, was injected into the left intermediolateral horn around the thoracolumbar junction, whereas a Cre-dependent viral vector encoding Channelrhodopsin2 under LoxP control was injected into the ipsilateral RVLM. In subsequent terminal experiments, blue laser light (473 nm × 20 ms pulses at 10 mW) was used to activate RVLM neurons that had been transduced by both vectors. Stimulus-locked activation, at appropriate latencies, was recorded in the following pairs of sympathetic nerves: forelimb and hindlimb muscle sympathetic fibres, as well as cardiac and either hindlimb muscle or lumbar sympathetic nerves. The latter result demonstrates that axon collaterals of lumbar-projecting RVLM neurons project to, and excite, both functionally similar (forelimb and hindlimb muscle) and functionally dissimilar (lumbar and cardiac) preganglionic neurons. Taken together, these findings show that the axons of a significant proportion of RVLM neurons collateralise widely within the spinal cord, and that they may excite preganglionic neurons of more than one functional class.
Topics: Animals; Autonomic Fibers, Preganglionic; Axons; Hindlimb; Interneurons; Male; Medulla Oblongata; Muscles; Neural Pathways; Neurons; Rats; Rats, Sprague-Dawley; Spinal Cord; Sympathetic Nervous System
PubMed: 31077360
DOI: 10.1113/JP277661 -
American Journal of Physiology.... May 2011Under acute and chronic conditions, the sympathetic nervous system can be activated in a differential and even selective manner. Activation of the rostral ventrolateral... (Comparative Study)
Comparative Study
Under acute and chronic conditions, the sympathetic nervous system can be activated in a differential and even selective manner. Activation of the rostral ventrolateral medulla (RVLM) has been implicated in differential control of sympathetic outputs based on evidence primarily in the cat. Although several studies indicate that differential control of sympathetic outflow occurs in other species, only a few studies have addressed whether the RVLM is capable of producing varying patterns of sympathetic activation in the rat. Therefore, the purpose of the present study was to determine whether activation of the RVLM results in simultaneous and differential increases in preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activities. In urethane-chloralose anesthetized rats, pre-ASNA, RSNA, and LSNA were recorded simultaneously in all animals. Microinjections of selected concentrations and volumes of glutamate increased pre-ASNA, RSNA, and LSNA concurrently and differentially. Pre-ASNA and RSNA (in most cases) exhibited greater increases compared with LSNA on a percentage basis. By varying the volume or location of the glutamate microinjections, we also identified individual examples of differential and selective activation of these nerves. Decreases in arterial pressure or bilateral blockade of RVLM GABA(A) receptors also revealed differential activation, with the latter having a 3- to 4-fold greater effect on sympathetic activity. Our data provide evidence that activation of the rat RVLM increases renal, lumbar, and preganglionic adrenal sympathetic nerve activities concurrently, differentially, and, in some cases, selectively.
Topics: Action Potentials; Adrenal Glands; Analysis of Variance; Anesthesia, General; Animals; Autonomic Fibers, Preganglionic; Bicuculline; Blood Pressure; Blood Vessels; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; GABA-A Receptor Antagonists; Glutamic Acid; Hindlimb; Kidney; Lumbosacral Plexus; Male; Medulla Oblongata; Microinjections; Muscle, Skeletal; Nitroprusside; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System; Time Factors; Vasodilator Agents
PubMed: 21346240
DOI: 10.1152/ajpregu.00713.2010 -
Scientific Reports Feb 2021Segmentation of axons in light and electron micrographs allows for quantitative high-resolution analysis of nervous tissues, but varied axonal dispersion angles result...
Segmentation of axons in light and electron micrographs allows for quantitative high-resolution analysis of nervous tissues, but varied axonal dispersion angles result in over-estimates of fiber sizes. To overcome this technical challenge, we developed a novel shape-adjusted ellipse (SAE) determination of axonal size and myelination as an all-inclusive and non-biased tool to correct for oblique nerve fiber presentations. Our new resource was validated by light and electron microscopy against traditional methods of determining nerve fiber size and myelination in rhesus macaques as a model system. We performed detailed segmental mapping and characterized the morphological signatures of autonomic and motor fibers in primate lumbosacral ventral roots (VRs). An en bloc inter-subject variability for the preganglionic parasympathetic fibers within the L7-S2 VRs was determined. The SAE approach allows for morphological ground truth data collection and assignment of individual axons to functional phenotypes with direct implications for fiber mapping and neuromodulation studies.
Topics: Animals; Axons; Female; Fixatives; Formaldehyde; Glutaral; Lumbosacral Region; Macaca mulatta; Microscopy, Electron; Nerve Fibers, Myelinated; Polymers; Spinal Nerve Roots; Tissue Fixation
PubMed: 33542368
DOI: 10.1038/s41598-021-82575-9