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Organization of the tonically active pathways through the superior cervical ganglion of the rabbit.

Responses of the neurons of the rabbit superior cervical ganglion to stimulation of the fascicles of preganglionic nerve fibres dissected from the cervical sympathetic trunk, and tonic activity of these neurons were recorded with intracellular electrodes in vitro and in vivo, respectively. It was found that on average 8.5 +/- 1.2 preganglionic fibres converge on each ganglion cell. In each preparation a single input spike could be evoked in a ganglion cell by stimulation of only one of all tested fascicles. The interspike intervals for single and multiple preganglionic inputs in tonic activity of ganglion neurons displayed Gaussian and Poisson distributions, respectively. The frequencies of spikes showing a Gaussian distribution correspond in most cases to pulse and respiratory frequencies. These data suggest that (1) single input is formed by a single preganglionic fibre which evokes EPSP of an amplitude high enough to trigger a postsynaptic spike, and that (2) regular activity of the ganglion neuron triggered by single input is probably due to a regular afferent drive. A cross-correlation analysis between the intracellular tonic activity and the tonic activity simultaneously recorded from the postganglionic nerve was made. The results of the analysis were compared with those obtained when intracellular spikes were evoked by stimulation of one particular neuron. From this comparison it has been concluded that about 100 ganglion cells, on the average, discharge synchronously within the 20-ms range during their tonic activity.

Animals↗

Peripheral nerve pathways to neurons in the guinea pig inferior mesenteric ganglion determined electrophysiologically after chronic nerve section.

Peripheral synaptic pathways to neurons in the guinea pig inferior mesenteric ganglion (IMG) were studied. Nerve trunks innervating neurons in the ganglion were surgically sectioned and intracellular electrical responses to nerve stimulation were measured 6-8 days after surgery. In all animals ganglia were decentralized by removal of the lumbar sympathetic chain ganglia L2 through L4 and in addition two peripheral nerves were sectioned leaving the ganglion innervated by only one peripheral nerve. Fast and slow excitatory postsynaptic potential (EPSP) were evoked with electrical stimulation of each of the nerve trunks and with distension of the colon. The thresholds to evoke fast EPSPs and the amplitude of slow EPSPs were compared for each nerve trunk among the different surgical groups including sham-operated controls and completely denervated ganglia. Both fast and slow EPSPs could be evoked electrically from each intact peripheral nerve trunk after the other three nerve trunks had been sectioned, which demonstrates that nerve fibers with cell bodies in the regions innervated by the peripheral nerves make functional synaptic connections with neurons in the inferior mesenteric ganglion. In general, nerve sections increased the threshold for evoking fast EPSPs and decreased the amplitude of electrically-evoked slow EPSPs compared to control ganglia. Synaptic potentials could also be evoked with stimulation of cut nerve trunks, demonstrating that branches of nerve fibers from peripheral nerves enter other nerve trunks. The hypogastric nerve was unique in that branches of axons eliciting fast but not slow synaptic potentials in the ganglion entered this nerve trunk. Distension-induced fast and slow EPSPs were present only if the lumbar colonic nerve was intact and they were not altered by section of the other nerve trunks. In contrast, the slow EPSPs evoked with electrical stimulation of the lumbar colonic nerve were significantly smaller when at least one other nerve trunk was sectioned suggesting that the axon branches from other nerve trunks which enter the lumbar colonic nerve are not activated by distension. These studies demonstrate that neurons eliciting either fast or slow synaptic potentials with cell bodies in regions innervated by the peripheral nerve trunks make functional synaptic connections with neurons of the inferior mesenteric ganglion. The results also suggest that the majority of mechanosensory neurons mediating excitatory synaptic responses to colon distension are neurons with a peripheral cell body.

Action Potentials↗

Origins of nerve terminals containing nitric oxide synthase in the guinea-pig coeliac ganglion.

Nitric oxide synthase was localised immunohistochemically and by NADPH diaphorase activity in two groups of nerve terminals and in rare cell bodies in the guinea-pig coeliac ganglion. Strongly reactive varicose terminals surrounded a subgroup of principal ganglion cells, most of which were in the medial lobes of the ganglion and most of which were somatostatin immunoreactive. A second set of varicose terminals, which were less intensely reactive, were found throughout the ganglia. Nitric oxide synthase containing nerve cell bodies in the intermediolateral cell columns of the spinal cord were labelled by dye retrogradely transported from the coeliac ganglion. Lesion of nerve connections between abdominal viscera and the coeliac ganglion caused a loss of the strongly reactive fibres, while the widely distributed, less intensely reactive fibres persisted. It is concluded that nitric oxide synthase terminals in the coeliac ganglion come from two sources, sympathetic preganglionic neurons and intestinofugal neurons.

Amidines↗

Developmental time course of the effect of nerve growth factor on the parasympathetic ciliary ganglion.

Neurite outgrowth in the presence and absence of nerve growth factor (NGF) was compared in neuronal cultures from the parasympathetic ciliary ganglion and from a traditional target of NGF, the sensory dorsal root ganglion. Both ciliary and dorsal root ganglion cultures exhibited a developmental time window during which the effect of NGF on neurite length was maximal. Although neuronal cultures from embryonic day 4 and 5 ganglia exhibited considerable neurite outgrowth in the absence of NGF, there was no significant increase in neurite outgrowth in the presence of NGF. After embryonic day 6, there was a steady increase in the effect of NGF in both types of ganglia. With ciliary ganglia, the effect of NGF increased until day 8, plateaued, then fell off significantly after day 11. With dorsal root ganglia, the effect of NGF continued to increase until day 12, plateaued, then fell off significantly after day 17. Thus, the period of maximal responsiveness of chick ciliary ganglia to NGF occurs earlier in development than for dorsal root ganglia. At the ages when the effect of NGF was maximal, approximately 20% of ciliary ganglion neurons exhibited substantial increases in neurite length compared to approximately 40% of dorsal root ganglion neurons. The effect of NGF was maximal at or below 1 ng/ml (4 X 10(-11) M) for both types of ganglia. These results support previous evidence that NGF does not simply boost ciliary ganglionic neurite growth non-specifically: the effect of NGF is already maximal at low, physiological concentrations and it appears at a specific time in development.

Animals↗

Partial down-regulation at post-transcriptional level of the gene expression for preproenkephalin in the superior cervical ganglion of the maturing rat.

In rats at the postnatal week 3 (P3W), enkephalin-immunoreactivity was detected in subsets of principal ganglion cells in the superior cervical ganglion and nerve fibers within the submandibular gland, one of the targets for the ganglion, whereas it disappeared from them at P8W. Enkephalin-immunoreactive ganglion cells and intraglandular fibers were detected again after the colchicine-pretreatment at P8W. By in situ hybridization the population density of ganglion cells expressing mRNA for preproenkephalin and the expression intensity were similar in both ganglia at P3W and P8W. These findings suggest that the post-transcriptional down-regulation of gene expression for preproenkephalin is involved in the disappearance of enkephalin-immunoreactivity in the adult ganglion.

Animals↗

Ultrastructure of the ganglion on human internal laryngeal nerve.

There is now definite evidence for the presence of a macroscopic ganglion on the human internal laryngeal nerve, with the distribution of its post-ganglionic fibres to the glands in the saccule and to the glands at the root of epiglottis in the vicinity of the opening of the saccule. This ganglion could be identified as early as 14 weeks in human foetal larynx, which contains immature neurons. Seven ganglia, dissected from human laryngectomy specimens and resected for carcinoma larynx, were studied by electron microscopy. Ultrastructurally, the neurons and the synaptic terminals had both small, round, luscent vesicles and dense core vesicles. Symmetrical, asymmetrical and electrical synaptic complexes were noted. A few neurons revealed degenerative changes suggestive of axotomy. The location of the ganglion on the internal laryngeal nerve, a branch of nervus vagus, and ultrastructural demonstration of large and small dense core vesicles and small luscent vesicles in the neurons of this ganglion, lead us to believe that the ganglion is parasympathetic in nature.

Adult↗

Aging rat vestibular ganglion: I. Quantitative light microscopic evaluation.

This study was undertaken to quantify age-related changes in the rat vestibular ganglion. Cell number, diameter, and proximal-distal distribution based on size were evaluated. Serial 5-microns plastic sections of the vestibular ganglion from 15 female Wistar rats were examined. Rats were divided into three age groups: young (Y, 3 to 5 months, n = 5), old (0, 24 to 26 months, n = 3), and very old (VO, 28 to 31 months, n = 7). Quantitative analysis indicated no significant differences (P less than .05) in the estimated number of ganglion cells (mean: Y = 1,690, 0 = 2,257, VO = 1,678), ganglion cell profile diameters (mean: Y = 22.5 microns, n = 2,886; O = 23.7 microns, n = 2,313; VO = 22.8 microns, n = 4,061), or proximal-distal localization (proximal: 22.3 microns, 24.4 microns, 22.7 microns; middle: 22.6 microns, 23.1 microns, 22.4 microns; distal: 23.3 microns, 23.4 microns, 23.7 microns; Y, O, and VO, respectively). When pooled, the old animals tended to have slightly larger cell profiles than the other groups. We noted a dramatic age-related increase of aging pigment within the ganglion cell profiles, making the old and very old animals easily distinguishable from the young. In most of the cell profiles, the aging pigment was more or less uniformly distributed throughout the cytoplasm. However, in some, aging pigment was accumulated at one pole of the cell profile. While no typical degenerating cellular profiles were found in any of the sections, several of the ganglion cell profiles from the old animals revealed dense cytoplasm, possibly indicating an early stage of degeneration.

Age Factors↗

Development of enkephalin in the rectum and ganglion of Remak of the chick.

Radioimmunoassay (RIA) and high performance liquid chromatography were used in combination with immunocytochemistry to study the development of met-enkephalin (Met-enk) in the rectum and the ganglion of Remak of the chicken. Met-enk was detected by RIA in the rectum at 5 days of incubation (d.i.). The concentration increased from 5-9 d.i. and did not change significantly thereafter. In contrast, the concentration of Met-enk in Remak's ganglion increased throughout the developmental period of study. Met-enk immunoreactivity first appeared in cell bodies in Remak's ganglion at 6 d.i. and in a small number of processes in the wall of the rectum. By 9 d.i., Remak's ganglion contained many immunoreactive cell bodies, some of which extended processes into the wall of the rectum in the region of the myenteric plexus. Varicosities were first seen in the rectum at 13 d.i. and increased in number and staining intensity with developmental age. The fact that immunoreactive cell bodies persist in Remak's ganglion throughout the course of development and send processes into the rectum suggests that a major portion of enkephalinergic innervation of the rectum is extrinsic. On the other hand, the presence of Met-enk immunoreactivity in both nerve cell bodies and processes in rectal explants stripped of Remak's ganglion suggests that this peptide is also contained in intrinsic neurons in the chick rectum.

Animals↗

gamma-Aminobutyric acid enhances the light response of ganglion cells in the trout pineal organ.

Electrical recordings from achromatic second order neurons of intact superfused pineal organs of the rainbow trout were used to investigate the role of gamma-aminobutyric acid (GABA) in the transmission of photoreceptor signals onto centrally projecting ganglion cells. Bath-applied GABA decreased the spike discharge rate of 98% of achromatic ganglion cells in a dose-dependent manner. GABA was also active if applied during synaptic blockade, demonstrating the presence of GABAergic receptors at the ganglion cell level. Responsiveness of ganglion cells to light was reversibly enhanced by GABA. The light response curve of ganglion cells, which was obtained by plotting spike rate versus light intensity, was significantly shifted to lower frequencies by GABA, indicating that GABA is an important inhibitory modulator of ganglion cell activity in the trout pineal organ.

Action Potentials↗

A sensitive period for ganglion cell degeneration and the formation of aberrant retino-fugal connections following tectal lesions in rats.

Rats of 0, 3, 5, 10 and 30 days of age received unilateral tectal lesions. After surviving for 150 days the retinal ganglion cell layer of the contralateral eye was examined for evidence of a ganglion cell loss. The retino-fugal projections of the eye contralateral to the lesion were studied in autoradiographs. In the animals operated at 0 days of age, 33% of the ganglion cells had degenerated but in animals operated at 5 days of age, 67% of the ganglion cells had degenerated. The animals operated at 30 days of age show no significant cell loss. An aberrant retinal projection to the lateral posterior nucleus of the thalamus was found only in animals operated at 0 and 3 days of age. The retinal projection to the thalamus was investigated in normal rats of 0, 3, 5 and 10 days of age using the anterograde transport of horseradish peroxidase. There was a conspicuous projection to the lateral posterior nucleus in animals of 0 and 3 days of age, but in the 5-day-old rat the retinal projection to the lateral posterior nucleus was very small and similar to the adult pattern. We conclude that transecting the tectal terminals of retinal ganglion cells causes the ganglion cells to degenerate, unless they are old enough to have formed sustaining collaterals. In addition, the tectal lesion removes a major tectal input to the lateral posterior nucleus and, if carried out within the first few days, leads to the preservation of the normally transient retinal projection to the lateral posterior nucleus, presumably by reducing competition between axon terminals.

Animals↗

Denervation-induced formation of adrenergic synapses in the superior cervical sympathetic ganglion of the rat and the enhancement of this effect by postganglionic axotomy.

A study has been made at the ultrastructural level of the effects of denervation and axotomy on the synapse population of the rat superior cervical ganglion. Superior cervical ganglia were subjected unilaterally to acute (survival, 48 h) or chronic preganglionic denervation (survival, 41-189 days) by cutting the cervical sympathetic trunk; in chronic denervation experiments regeneration of preganglionic nerve fibres into the ganglion was prevented by suturing the proximal (caudal) stump of the trunk into the sternomastoid muscle. In some chronic experiments the preganglionic denervation was combined with simultaneous crush axotomy of the major postganglionic branches of the ganglion, the internal and external carotid nerves (axotomized-denervated ganglia). Control observations were made in contralateral ganglia and in ganglia from normal rats. After excision and before fixation, ganglia were incubated briefly in the presence of 5-hydroxydopamine to label adrenergic vesicles. Chronic denervation caused a statistically significant 12% decrease from control values in the cytoplasmic minor axes of the principal ganglionic neurones; axotomy combined with chronic denervation led to a 6% increase in this dimension, which was not statistically significant. The minor axes of the neuronal nuclei did not differ significantly from control values in either type of experiment. Axotomy combined with denervation led however to a 36% decrease in the incidence of nucleated neuronal profiles per unit area of ganglion. Counts of synapses were made in the various classes of ganglia and their incidence was expressed per nucleated neuronal profile, to permit comparison within and between experiments. Normal and control ganglia showed a high incidence of synapses of preganglionic cholinergic type. Nerve terminal profiles and synapses containing small dense-cored vesicles, as distinct from the efferent synapses of small granule-containing cells, were not found to be present on the principal neurones or their dendrites in these ganglia, despite strong 5-hydroxydopamine labelling of small dense-cored vesicles within cell bodies and dendrites. After acute denervation extremely few residual synapses were found in the ganglion, in areas remote from small granule-containing cells, and these residual synapses were of the cholinergic type. Acute denervation led to the appearance of vacated or isolated postsynaptic densities; such densities were also found, but were fewer in number, in chronically denervated and axotomized-denervated ganglia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Maturation of opioid sensitivity of fetal mouse dorsal root ganglion neuron perikarya in organotypic cultures: regulation by spinal cord.

Opioid agonists selectively decrease the duration of the Ca2+ component of the action potential recorded from embryonic dorsal root ganglion neurons in dissociated cell cultures. In contrast, no significant alterations in the action potentials generated by adult dorsal root ganglion neurons in vivo were detected during opioid exposure. In the present study, the perikaryal opioid sensitivity of fetal mouse dorsal root ganglion neurons was analyzed during maturation in organotypic explant cultures. To determine whether spinal cord might influence this sensitivity, neuron perikarya were tested in ganglia grown: (a) in isolation; (b) attached to spinal cord explants; and (c) attached to spinal cord, but decentralized by a dorsal root transection in mature explants 1-2 weeks before the tests. After 2-8 weeks in culture, the duration of the Ba2+-enhanced Ca2+ component of intracellularly recorded action potentials was measured prior to and during bath exposure to the opioid, [D-Ala2, D-Leu5]enkephalin. Sensitive neurons were characterized by a marked, reversible reduction (averaging about 50%) in the duration of the Ca2+ component (which was antagonized by naloxone). The fraction of opioid-sensitive neuron perikarya in dorsal root ganglia grown attached to cord explants was significantly lower (48%) than in ganglia grown isolated (78%) or decentralized in vitro (79%). The mean duration of the Ca2+ component was significantly shorter in ganglion cells which had been grown attached to cord, or subsequently decentralized, compared to cells grown in isolated ganglia (by 24 and 38%, respectively). This difference was even larger in the opioid-insensitive groups. Although opioid-sensitive perikarya in ganglia grown attached to cord had a significantly longer Ba2+-enhanced Ca2+ component than that of insensitive neurons, some of the insensitive perikarya in all 3 types of explant paradigms displayed Ca2+ components which were as prolonged as those of sensitive cells. The results obtained in this study support the hypothesis that the observed decrease in the fraction of opioid-sensitive perikarya during development of fetal mouse dorsal root ganglia is due to regulation by interactions with their central target tissue, the spinal cord. The developmental decrease in the duration of the Ca2+ component of the action potential of these ganglion cells is also enhanced by the presence of the spinal cord. However, regulation of functional opiate receptors and Ca2+ component duration of the ganglion cell perikarya appear to be independent processes.

Action Potentials↗

Development of cholinergic traits in the quail ciliary ganglion: expression of choline acetyltransferase-like immunoreactivity.

The avian ciliary ganglion is a parasympathetic ganglion derived from the neural crest whose neurons provide cholinergic innervation to the eye. Here, we describe the time course of appearance and the morphology of cholinergic cells in the ciliary ganglion, as assessed by antibodies against choline acetyltransferase. Choline acetyltransferase immunoreactivity was first observed in 5.5-day-old quail embryos, 1 day after condensation of the ciliary ganglion. Both the intensity of choline acetyltransferase immunoreactivity and size of the choline acetyltransferase-immunoreactive cells increased with ganglionic age. By 12 days, a second population of choline acetyltransferase-immunoreactive cells, possibly corresponding to choroid neurons, was observed whose cells were smaller and less intensely stained than earlier differentiating choline acetyltransferase-immunoreactive cells. The percentage of choline acetyltransferase-immunoreactive cells was initially high, constituting approximately 50% of the total cell population. As a function of time, the proportion of cholinergic cells decreased, probably due to proliferation of non-neuronal cells and naturally-occurring cell death. Our results confirm the existence of two morphologically distinct populations of cholinergic neurons in the avian ciliary ganglion and demonstrate that these neuronal subpopulations express choline acetyltransferase immunoreactivity at different times in development. Because choroid neurons innervate their targets later than ciliary neurons, this finding is consistent with the hypothesis that target interactions regulate expression of choline acetyltransferase.

Animals↗

Comparison of immunohistochemical localization of [Met5] enkephalin-Arg6-Gly7-Leu8, vasoactive intestinal polypeptide and tyrosine hydroxylase in the major pelvic ganglion of the rat.

The major pelvic ganglion is an autonomic ganglion containing both sympathetic and parasympathetic postganglionic neuronal cell bodies. The existence of the proenkephalin A-derived peptide [Met5]enkephalin-Arg6-Gly7-Leu8 immunoreactivity in the rat major pelvic ganglion has been described quite recently. The aim of this study was to compare the relations of [Met5]enkephalin-Arg6-Gly7-Leu8-containing postganglionic neurons and nerve fibers to noradrenergic (tyrosine hydroxylase-immunoreactive) and non-noradrenergic (putative cholinergic) neurons of the rat major pelvic ganglion. Immunohistochemical double staining and elution-restaining techniques were used to investigate the distribution of [Met5]enkephalin-Arg6-Gly7-Leu8 in correlation with tyrosine hydroxylase and vasoactive intestinal polypeptide. The major pelvic ganglion contained neurons immunoreactive either for tyrosine hydroxylase or vasoactive intestinal polypeptide. Many principal neurons, however, were immunoreactive for tyrosine hydroxylase nor vasoactive intestinal polypeptide. [Met5]Enkephalin-Arg6-Gly7-Leu8-immunoreactive principal neurons formed a minor subpopulation in the ganglion and were not immunoreactive for tyrosine hydroxylase. The majority of [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive principal cells were non-immunoreactive for vasoactive intestinal polypeptide, but a few of them also contained vasoactive intestinal polypeptide. In contrast to the large [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive principal neurons, which formed a population of non-noradrenergic (putative cholinergic) cells, the small [Met5]enkephalin-Arg6-Gly7-Leu8-immunoreactive cell exhibited intense tyrosine hydroxylase immunofluorescence and represented a subpopulation of small, intensely fluorescent cells. [Met5]Enkephalin-Arg6-Gly7-Leu8-immunoreactive pericellular fiber plexuses were found around tyrosine hydroxylase- and vasoactive intestinal polypeptide-immunoreactive principal neurons and in association with small intensity fluorescent cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biogenic amine localization in cardiac ganglion intrinsic neurons: electron microscopic histochemistry of SIF cells.

The parasympathetic cardiac ganglion in the mudpuppy, N. maculosus, contains postganglionic nerve cells and intrinsic neurons, many of which are small intensely fluorescent (SIF) cells. Several bioactive substances have been localized in the intrinsic nerve cells which may have integrative effects at synapses within the ganglion. Ganglionic intrinsic neurons can be identified electron microscopically by the presence of numerous cytoplasmic granular vesicles 80-120 nm in diameter. Throughout the ganglion there are bundles of unmyelinated fibers some of which are filled with granular and agranular vesicles and axosomatic terminals with similar vesicles synapsing on principal parasympathetic nerve cells. To understand the aminergic contribution to ganglionic synaptic circuitry the chromaffin reaction was used. The intrinsic neurons (i.e., SIF cells) were readily identified by their characteristic intracellular granule population. All intrinsic nerve cells identified showed granules which were positively labelled by the chromaffin reaction. Granular vesicles in synaptic profiles on principal cells (P cells) were also labelled indicating a direct aminergic synaptic innervation to these cells. The cell bodies of intrinsic neurons, ensheathed with supportive glial-like cellular processes, rarely received synapses. Elemental microanalysis was used to verify the chromium content of the electron dense product within the granular vesicles. These studies demonstrated direct aminergic synaptic input to at least a subpopulation of principal parasympathetic cells in the cardiac ganglion of mudpuppy.

Animals↗

Studies on the crustacean cardiac ganglion.

1. An overview of studies on the decapod crustacean cardiac ganglion is given emphasizing contributions to questions of general interest in cellular neurophysiology. 2. John Welsh, in 1951, introduced this 9-celled, semi-autonomous ganglion as a preparation offering physiologists unique experimental possibilities. 3. It exhibits remarkable reliability and stability in rhythmic pattern generation. The neurons show endogenous burst-forming capability mediated by "driver potentials". 4. These regenerative, Ca-mediated potentials are restricted to the soma, while impulse-generating membrane is segregated to the distal axon. 5. Thus, voltage-clamp analysis of the ionic currents underlying the burst-forming potentials is possible by isolating the soma with a ligature. 6. The isolated ganglion is spontaneously active, but the normal mechanism of pacemaking remains to be clarified, including the possible contribution of stretch-sensitive dendrites. 7. The activity of the ganglion is subject to modulation by neurohumors. These include the transmitter at intraganglionic synapses, transmitters of the pair of inhibitory and the two pairs of acceleratory fibers, and neurohormones released from the pericardial organs. The transmitters are not established. 8. Effects on the ganglion of substances isolated from the pericardial organs have been described. 9. These include 5-hydroxytryptamine, dopamine, octopamine, and two peptides. 10. One of these, proctolin, produces a long-lasting sequence of effects. 11. The work continues to raise new questions for which the ganglion offers excellent research material.

Animals↗

Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation.

BACKGROUND: Numerous reports have demonstrated an association between autonomic tone and atrial fibrillation (AF). Pulmonary vein (PV) denervation during catheter ablation of AF has been shown to significantly reduce recurrence of AF. OBJECTIVES: The purpose of this study was to assess the safety and efficacy of high-frequency stimulation at mapping cardiac ganglionated plexuses in patients undergoing catheter ablation of AF. METHODS: Fourteen patients with a history of symptomatic AF underwent a single transseptal approach and electroanatomic mapping of the left atrium, right atrium, and coronary sinus. Using high-frequency stimulation with patients under general anesthesia (20-50 Hz, 5-15 V, pulse width 10 ms), mapping of ganglionated plexuses was performed. Radiofrequency (RF) ablation was performed during AF guided by complex fractionated atrial electrograms. Lesions were mostly delivered circumferentially in the antral area of the PVs, predominantly over and adjacent to regions of ganglionated plexuses. RESULTS: There was a mean of 4 +/- 1 (range 2-6) ganglionated plexuses per patient, and a mean total of 3 +/- 1 RF applications were delivered over positive vagal sites. Although a vagal response occurred infrequently during ablation (0.9%), postablation high-frequency stimulation failed to provoke a vagal response in 30 (88%) of 34 previously positive vagal sites that underwent ablation. CONCLUSION: Ganglionated plexuses can be precisely mapped using high-frequency stimulation and are located predominantly in the path of lesions delivered during ablation of AF. Objective documentation of modification of autonomic tone can be documented in the majority of patients. Future studies are required to determine the specific role of mapping and targeting of ganglionated plexuses in patients undergoing catheter ablation of AF.

Adult↗

Inhibitory M2 muscarinic receptors are upregulated in both axotomized and intact small diameter dorsal root ganglion cells after peripheral nerve injury.

Acetylcholine reduces nociceptive input in part by activating inhibitory M2 muscarinic receptors on primary sensory neurons, and acetylcholinesterase inhibitors and muscarinic agonists produce analgesia in humans and animals. M2 muscarinic receptors are upregulated in animals with diabetic neuropathy, but their level of expression and function after peripheral nerve injury has not been previously examined. This study tested, using intracellular Ca(2+) response to membrane depolarization, the effect of the M2 muscarinic receptor agonist bethanechol on individual dorsal root ganglion cells from normal and L5-6 spinal nerve-ligated rats, followed by M2 muscarinic receptor immunostaining. We also examined functional transient receptor potential for vanilloids-1 activity by determining intracellular Ca(2+) response evoked by capsaicin in M2 muscarinic receptor immunoreactive cells. In normal dorsal root ganglion cells, bethanechol inhibited the Ca(2+) response in a concentration-related fashion, and this inhibition was blocked by the M2 muscarinic receptor antagonist gallamine. Cells expressing M2 muscarinic receptors by immunostaining were significantly inhibited by bethanechol, whereas those lacking positive staining were not. The proportion of studied dorsal root ganglion neurons with positive M2 muscarinic receptor staining increased significantly in the injured ipsilateral L5-6 and the uninjured ipsilateral L4 ganglia, but not in the contralateral dorsal root ganglion neurons compared with normals. In contrast, the proportion of neurons responding to capsaicin significantly decreased in the injured ipsilateral L5-6 dorsal root ganglion cells. These results suggest that inhibitory M2 muscarinic receptors are upregulated in small- and medium-sized axotomized dorsal root ganglion neurons and their uninjured neighbors following nerve injury, and may represent an appropriate target for analgesia in this setting.

Animals↗