Postganglionic Parasympathetic Neurons Research Articles

Heart failure-induced changes of voltage-gated Ca2+ channels and cell excitability in rat cardiac postganglionic neurons

Chronic heart failure (CHF) is characterized by decreased cardiac parasympathetic and increased cardiac sympathetic nerve activity. This autonomic imbalance increases the risk of arrhythmias and sudden death in patients with CHF. We hypothesized that the molecular and cellular alterations of cardiac postganglionic parasympathetic (CPP) neurons located in the intracardiac ganglia and sympathetic (CPS) neurons located in the stellate ganglia (SG) possibly link to the cardiac autonomic imbalance in CHF. Rat CHF was induced by left coronary artery ligation. Single-cell real-time PCR and immunofluorescent data showed that L (Ca(v)1.2 and Ca(v)1.3), P/Q (Ca(v)2.1), N (Ca(v)2.2), and R (Ca(v)2.3) types of Ca2+ channels were expressed in CPP and CPS neurons, but CHF decreased the mRNA and protein expression of only the N-type Ca2+ channels in CPP neurons, and it did not affect mRNA and protein expression of all Ca2+ channel subtypes in the CPS neurons. Patch-clamp recording confirmed that CHF reduced N-type Ca2+ currents and cell excitability in the CPP neurons and enhanced N-type Ca2+ currents and cell excitability in the CPS neurons. N-type Ca2+ channel blocker (1 μM ω-conotoxin GVIA) lowered Ca2+ currents and cell excitability in the CPP and CPS neurons from sham-operated and CHF rats. These results suggest that CHF reduces the N-type Ca2+ channel currents and cell excitability in the CPP neurons and enhances the N-type Ca2+ currents and cell excitability in the CPS neurons, which may contribute to the cardiac autonomic imbalance in CHF.

Intrapancreatic ganglia neurons receive projection fibers from melanocortin-4 receptor-expressing neurons in the dorsal motor nucleus of the vagus nerve of the mouse

Melanocortin-4 receptor (MC4R)-expressing neurons are widely distributed in the central nervous system and play a crucial role in a variety of physiological functions including energy and glucose/insulin homeostasis. However, their neural pathways remain to be elucidated. In the present study, we examined a possible pathway from MC4R-expressing neurons in the dorsal motor nucleus of the vagus nerve (DMV) to the intrapancreatic ganglia using transgenic mice that express green fluorescent protein (GFP) under the control of the MC4R-promoter. Using immunofluorescence labeling, we demonstrated that GFP-immunoreactive (ir) nerve fibers were distributed in the intrapancreatic ganglia closely associated with the islets as well as among the acini. These GFP-ir fibers with bouton-like varicosities were frequently observed to surround ganglion cells immunoreactive for vasoactive intestinal polypeptide, a marker for postganglionic parasympathetic neurons. Using the pre-embedding immunoperoxidase method, we clearly showed that GFP-ir terminals formed synapses predominantly with dendrites and additionally with somata of the ganglion cells. Moreover, bilateral subdiaphragmatic vagotomy caused a marked loss of GFP immunoreactivity in the pancreas. Using a combination of retrograde tracing and immunohistochemistry, we finally demonstrated that nearly half of the pancreas-projecting DMV neurons were immunoreactive for GFP. These results suggest that MC4R-expressing DMV neurons may participate in the regulation of glucose/insulin homeostasis through their projections to the intrapancreatic ganglia.

Similar effects of vagus nerve stimulation and atrial ganglionated plexi stimulation on ventricular effective refractory period and action potential duration in canine

Cervical vagus nerves and atrial ganglionated plexi (GP) serve as the main extrinsic and intrinsic cardiac parasympathetic nervous systems [1], respectively. Atrial GP have been found to be concentrated within epicardial fat pads. Although atrial GP are traditionally considered as relay stations that merely transmit central parasympathetic impulses to the heart, recent studies indicated that GP included not only parasympathetic postganglionic neurons but also sympathetic neurons and the innervation by a host of neurochemically non-cholinergic inputs [2], going well beyond cholinergic efferent neuronal relay stations.

Immunoreactivity for Choline Acetyltransferase of Peripheral-Type (pChAT) in the Trigeminal Ganglion Neurons of the Non-Human Primate <i>Macaca fascicularis</i>

Transcripts of the choline acetyltransferase (ChAT) gene reveal a number of different splice variants including ChAT of a peripheral type (pChAT). Immunohistochemical staining of the brain using an antibody against pChAT clearly revealed peripheral cholinergic neurons, but failed to detect cholinergic neurons in the central nervous system. In rodents, pChAT-immunoreactivity has been detected in cholinergic parasympathetic postganglionic and enteric ganglion neurons. In addition, pChAT has been observed in non-cholinergic neurons such as peripheral sensory neurons in the trigeminal and dorsal root ganglia. The common type of ChAT (cChAT) has been investigated in many parts of the brain and the spinal cord of non-human primates, but little information is available about the localization of pChAT in primate species. Here, we report the detection of pChAT immunoreactivity in trigeminal ganglion (TG) neurons and its co-localization with Substance P (SP) and/or calcitonin gene-related peptide (CGRP) in the cynomolgus monkey, Macaca fascicularis. Neurons positive for pChAT were observed in a rather uniform pattern in approximately half of the trigeminal neurons throughout the TG. Most pChAT-positive neurons had small or medium-sized cell bodies. Double-immunofluorescence staining showed that 85.1% of SP-positive cells and 74.0% of CGRP-positive cells exhibited pChAT immunoreactivity. Most pChAT-positive cells were part of a larger population of neurons that co-expressed SP and/or CGRP.

Galanin Expression in the Mouse Major Pelvic Ganglia During Explant Culture and Following Cavernous Nerve Transection

Autonomic neurons commonly respond to injury/axotomy with an increased expression of neuropeptides including galanin and pituitary adenylyl cyclase-activating polypeptide (PACAP). The increased peptide expression may enhance neuronal survival and axonal regeneration. Using quantitative (Q) PCR and immunocytochemistry, the present study tested whether galanin expression increased in male mouse major pelvic ganglia (MPG) neurons in response to injury. Galanin transcript expression increased significantly in MPG neurons following 72 h in explant culture and 72 h after unilateral transection of the cavernous nerve. Under both conditions, the increase in galanin transcript levels was greater than the increase in PACAP transcript levels. In control MPG, galanin-IR nerve fibers formed pericellular arrangements around MPG neurons although few galanin-IR cells were evident and many of the galanin-IR cells may be small intensely fluorescent (SIF) cells. In 3-day-cultured MPGs, many more galanin-IR cells and nerve fibers were noted. The increased galanin expression was most apparent in neurons that were also immunoreactive for neuronal nitric oxide synthase, rather than tyrosine hydroxylase. Some explant-cultured MPG neurons exhibited immunoreactivity to galanin and PACAP. As reported previously for PACAP, there is an injury-induced increase in MPG galanin expression, which occurs preferentially in the parasympathetic postganglionic neurons.

Effect of OnabotulinumtoxinA on Intramural Parasympathetic Ganglia: An Experimental Study in the Guinea Pig Bladder

We investigated whether onabotulinumtoxinA injected in the bladder would affect preganglionic parasympathetic nerve endings in intramural ganglia. Guinea pig bladders were injected with 5 U of botulinum toxin. At 24 hours bladders were collected and processed for immunohistochemistry using tyrosine hydroxylase, and intact and cleaved SNAP-25. To identify the different populations of affected fibers coursing the ganglia we performed double immunoreactions for cleaved SNAP-25 and VAChT, TH or CGRP. VAChT immunoreactive fibers were identified in axons and varicosities of presynaptic to postganglionic parasympathetic neurons. Those fibers were also immunoreactive to SV2 and SNAP-25. The rare CGRP and TH immunoreactive fibers coursing in the ganglia did not express SV2 or SNAP-25. After onabotulinumtoxinA injection the cleaved form of SNAP-25 was abundantly expressed in parasympathetic fibers. Botulinum toxin injection in the bladder wall affects preganglionic parasympathetic nerve terminals. This could contribute to the strong effect of botulinum toxin on bladder smooth muscle activity.

Transmission of impulses in the parasympathetic cardiomotor pathway to the sino-atrial node

In mammals and other vertebrates the pacemaker cells of the sino-atrial (SA) node are under powerful inhibitory control of parasympathetic postganglionic cardiomotor neurones. The preganglionic neurones are located in the nucleus ambiguus; some are also located in the dorsal motor nucleus of the vagus although their function in the regulation of pacemaker activity is unknown (Jones, 2001). Activation of these preganglionic cardiomotor neurones leads to activation of cholinergic postganglionic neurones in cardiac ganglia, which in turn results in inhibition of the pacemaker cells in the SA node and subsequently in a decrease of heart rate. It is universally propagated in textbook chapters and elsewhere that the synaptic transmission from parasympathetic preganglionic neurones to postganglionic neurones in the cardiac ganglia occurs with a high safety factor without modulation and that the inhibition of pacemaker cells by activation of cholinergic cardiomotor neurones is mainly generated by the opening of potassium channels via the second-messenger adenylate cyclase/cAMP pathway and by suppression of hyperpolarization-activated Na+/K+-channels. These assumptions need to be corrected in view of experimental data published previously and recently.

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 μM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.

5‐HT1D Receptor Immunoreactivity in the Sphenopalatine Ganglion: Implications for the Efficacy of Triptans in the Treatment of Autonomic Signs Associated With Cluster Headache

To determine if 5-HT(1D) receptors are located in the sphenopalatine ganglion. While the 5-HT(1D) receptor has been described in sensory and sympathetic ganglia in the head, it was not known whether they were also located in parasympathetic ganglia. We used retrograde labeling combined with immunohistochemistry to examine 5-HT(1D) receptor immunoreactivity in rat sphenopalatine ganglion neurons that project to the lacrimal gland, nasal mucosa, cerebral vasculature, and trigeminal ganglion. We found 5-HT(1D) receptor immunoreactivity in nerve terminals around postganglionic cell bodies within the sphenopalatine ganglion. All 5-HT(1D) -immunoreactive terminals were also immunoreactive for calcitonin gene-related peptide but not vesicular acetylcholine transporter, suggesting that they were sensory and not preganglionic parasympathetic fibers. Our retrograde labeling studies showed that approximately 30% of sphenopalatine ganglion neurons innervating the lacrimal gland, 23% innervating the nasal mucosa, and 39% innervating the trigeminal ganglion were in apparent contact with 5-HT(1D) receptor containing nerve terminals. These data suggest that 5-HT(1D) receptors within primary afferent neurons that innervate the sphenopalatine ganglion are in a position to modulate the excitability of postganglionic parasympathetic neurons that innervate the lacrimal gland and nasal mucosa, as well as the trigeminal ganglion. This has implications for triptan (5-HT(1D) receptor agonist) actions on parasympathetic symptoms in cluster headache.

Innervation of parasympathetic postganglionic neurons and bladder detrusor muscle directly after sacral root transection and repair using nerve transfer

This is a continuation of studies examining the effectiveness of root repairs and nerve transfers for bladder reinnervation. Our previous retrograde fluorogold tracing studies from the bladder to the spinal cord found regrowth of axons from the spinal cord through the nerve repair site to the bladder which was confirmed electrophysiologically [Ruggieri et al. J Neurotrauma 25:214–24, 2006]. The current study determines whether the pattern of axonal regrowth from the repaired nerves or roots to the bladder is different between the surgical reanastomosis methods. The canine bladder was denervated by transection of all nerve roots from the sacral spinal cord mediating bladder contraction. Reinnervation surgeries included end-on-end repair of transected sacral ventral roots, transfer of coccygeal to sacral ventral roots(CGNT),or transfer of genitofemoral to pelvic nerves(GFNT). Postmortem dialkylcarbocyaninedye tracing with Neurotrace DiI from the distal pelvic nerve to the bladder wall, combined with PGP9.5 neuronal immunohistochemistry, demonstrated innervation by DiI-labeled axons of only parasympathetic postganglionic intramural ganglia in normal controls and sham operated controls, but reinnervation of both intramural ganglia and detrusor muscle directly after repair of sacral ventral roots. GF NT and CG NT also resulted in reinnervation of both intramural ganglia and detrusor muscle, although to a lesser extent than repaired roots. Bladder reinnervation with either the same nerve (orthotopic reinnervation) or with either a primarily somatic nerve (coccygeal) or a primarily sensory nerve (genitofemoral) results in reinnervation of both intramural ganglia as well as direct innervation of detrusor muscle.

PACAP Expression in Explant Cultured Mouse Major Pelvic Ganglia

The major pelvic ganglia (MPG) contain both parasympathetic and sympathetic postganglionic neurons and provide much of the autonomic innervation to urogenital organs and components of the lower bowel. Whereas many parasympathetic neurons were found to express vasoactive intestinal polypeptide (VIP), no MPG neurons exhibited immunoreactivity for pituitary adenylate cyclase-activating polypeptide (PACAP). However, in 3-day cultured MPGs, numerous PACAP-IR cells and nerve fibers were present, and transcript levels for PACAP increased significantly. In 3-day cultured MPGs, PACAP immunoreactivity was seen in cells that were also immunoreactive for VIP or neuronal nitric oxide synthase, but not tyrosine hydroxylase, indicating that PACAP expression occurred preferentially in MPG parasympathetic postganglionic neurons. Transcript levels for the VPAC2, but not VPAC1 or PAC1 receptor, also increased significantly following 3days in culture. Transcript levels of activating transcription factor 3 (ATF-3), a marker of cellular injury, were increased 64-fold in 3-day explants, and ATF-3-IR nuclei were evident in both TH-IR and nNOS-IR neurons as well as in non-neuronal cells. In sum, these results demonstrate that, although only the parasympathetic neurons in explant cultured MPGs increase expression of PACAP, both sympathetic and parasympathetic postganglionic neurons in the cultured MPG whole-mount increase expression of ATF-3.

Aspects of Datura poisoning and treatment

Introduction. Datura species, especially Datura stramonium (e.g., jimsonweed), are the focus of scores of case reports that chronicle the toxidrome of anticholinergic toxicity. Mechanisms of toxicity. Toxicity occurs because of the presence of up to 28 belladonna alkaloids, predominated by atropine and scopolamine. There are significant interspecies differences in the ratio of the belladonna alkaloids, atropine to scopolamine, and the presence of at least 26 other related alkaloids will vary, even between and among specimens of the same species. The differences may account for unexpected dose–response effects that are observed in some patients and even different profiles of toxicity. All parts of the Datura species contain belladonna alkaloids; in decreasing order, the belladonna alkaloid content is generally the greatest in the petioles (flowers), stem, fruit (seeds), leaves, and roots. Features. The most prominent symptoms are due to the blockade of peripheral muscarinic receptors that innervate exocrine glands, smooth muscle, and cardiac tissue. Therefore, the primary toxic manifestations include mydriasis, which is due to the blockade of papillary sphincter muscle and iris muscle; dry mouth, secondary to parasympathetic blockade of salivary secretion; tachycardia, caused by competition at muscarinic receptors in postganglionic parasympathetic neurons and blockade of receptors in the SA node; and fever and erythema, because of vasodilation and inhibition of sweating. Direct ocular exposure. Well known to produce mydriasis after ingestion, Datura is also notorious for producing maladies such as “gardeners eye” and “cornpickers eye,” which is a testament to the high concentrations of belladonna alkaloids in the entire plant. When the sap or dried plant material from a member of the Datura species enters the eye directly, the papillary sphincter and ciliary muscles are affected resulting in mydriasis and cycloplegia. Pupil dilation is sudden in onset and often profound. In a dose–response fashion, the mydriasis and its persistence will be dependent on the alkaloidal content and quantity of the sap. The mydriasis can be bilateral, but most commonly it is unilateral, which is frightening to the victim and to the clinician and suggestive of significant cerebral pathology. Management. As with any toxic exposure, the foundation of patient management is supportive care and patient reassurance. Because of the central nervous system effects of the belladonna alkaloids, the patient may be agitated, combative, confused, and disoriented. Initial intervention focuses on addressing those issues that protect the patient and their caregivers. In severe cases, physostigmine, a cholinesterase inhibitor, should be used to reverse anticholinergic toxicity. Physostigmine should be given intravenously to an adult in a dose of 0.5–2.0 mg at a rate of no more than 1 mg/min; a second dose may be administered if necessary. Children should receive 0.02 mg/kg intravenously and the rate should not exceed 0.5 mg/min. Extracorporeal elimination and forced diuresis of the belladonna alkaloids are not viable options. Conclusions. Members of the Datura species contain abundant amounts of belladonna alkaloids that can produce both local and systemic anticholinergic toxicity. Fatalities because of Datura species exposure are rare, but adverse effects are very common. Treatment is supportive with the use of physostigmine in more severe cases of poisoning.

Characterization of the Vagal Motor Neurons Projecting to the Guinea Pig Airways and Esophagus

Distinct parasympathetic postganglionic neurons mediate contractions and relaxations of the guinea pig airways. We set out to characterize the vagal inputs that regulate contractile and relaxant airway parasympathetic postganglionic neurons. Single and dual retrograde neuronal tracing from the airways and esophagus revealed that distinct, but intermingled, subsets of neurons in the compact formation of the nucleus ambiguus (nAmb) innervate these two tissues. Tracheal and esophageal neurons identified in the nAmb were cholinergic. Esophageal projecting neurons also preferentially (greater than 70%) expressed the neuropeptide CGRP, but could not otherwise be distinguished immunohistochemically from tracheal projecting preganglionic neurons. Few tracheal or esophageal neurons were located in the dorsal motor nucleus of the vagus. Electrical stimulation of the vagi in vitro elicited stimulus dependent tracheal and esophageal contractions and tracheal relaxations. The voltage required to evoke tracheal smooth muscle relaxation was significantly higher than that required for evoking either tracheal contractions or esophageal longitudinal striated muscle contractions. Together our data support the hypothesis that distinct vagal preganglionic pathways regulate airway contractile and relaxant postganglionic neurons. The relaxant preganglionic neurons can also be differentiated from the vagal motor neurons that innervate the esophageal striated muscle.

Neurotransmitters in Airway Parasympathetic Neurons Altered by Neurotrophin-3 and Repeated Allergen Challenge

Changes in airway nerves associated with chronic inflammation may underlie the pathogenesis and symptoms of lower airway diseases, such as asthma. The molecules most likely causing such alterations are neurotrophins (NTs) and/or related neurokines. In several species, including humans, lower airway parasympathetic postganglionic neurons that project axons to airway smooth muscle are either cholinergic or nonadrenergic noncholinergic (NANC), the latter synthesizing vasoactive intestinal peptide and nitric oxide, but not acetylcholine. In guinea pig trachealis smooth muscle, cholinergic nerve terminals arise from ganglionic neurons located near the tracheal smooth muscle, whereas the source of NANC nerve fibers is from neurons in ganglia located in the adjacent myenteric plexus of the esophagus, making this an ideal species to study regulation of parasympathetic neurotransmitter phenotypes. In the present study, we determined that, 48 hours after repeated allergen challenge, the NANC phenotype of airway parasympathetic ganglionic neurons changed to a cholinergic phenotype, and NT-3 mimicked this change. Nerve growth factor, brain-derived neurotrophic factor, leukemia inhibitory factor, or IL-1β had no effect on either phenotype, and they did not induce these neurons to synthesize substance P or tyrosine hydroxylase. These results indicate a role for inflammation and NT-3 in regulating biochemical and anatomical characteristics of principal neurons in adult airway parasympathetic ganglia.

Neural substrate of depression during migraine

Migraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn and thalamus. We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as stress activate multiple hypothalamic, limbic and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression and the quest for solitude. The network of bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive mechanism of perpetual feedback that drives a migraine attack for many hours and even days.

Role of Spinal Cav2.2 and Cav2.1 Ion Channels in Bladder Nociception

High voltage activated calcium channels have been implicated in nociceptive transmission in several animal pain models. To our knowledge this is the first study to evaluate the ability of various high voltage activated calcium channel blockers to inhibit the transmission of noxious stimuli from the bladder at the level of the spinal cord. The nociceptive response was measured by analyzing the visceromotor reflex and cardiovascular (pressor) responses to bladder distention. The role of Cav2.2 (N-type), Cav2.1 (P/Q-type) and Cav1 (L-type) calcium channels in bladder nociceptive reflex responses was examined using omega-conotoxin-GVIA, omega-agatoxin IVA/omega-conotoxin MVIIC and verapamil (Sigma-Aldrich), respectively. Female Sprague-Dawley rats were acutely instrumented with intrathecal catheters, carotid arterial and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectric activity subsequent to repeat phasic bladder distention at 60 mm Hg for 30 seconds at 3-minute intervals with the rats under 1% isoflurane. Drugs were administered by intrathecal injection 2 minutes before distention and responses were recorded for 15 minutes per dose. When administered intrathecally, omega-conotoxin-GVIA and omega-conotoxin MVIIC (10 microg/kg each) significantly attenuated reflex responses to noxious bladder distention to 12% and 65% of the maximal visceromotor reflex response, and to 45% and 59% of the control pressor response, respectively. However, agatoxin and verapamil were less effective. The study suggests that spinal Cav2.2 and Q-type Cav2.1 calcium channels contribute to acute bladder nociception, while Cav1 channels have a limited role.

Remodeling of the guinea pig intracardiac plexus following pressure overload‐induced cardiac hypertrophy

Chronic pressure overload (PO) of guinea pig hearts was induced by a banding of the descending dorsal aorta (10–15% constriction). Animals were allowed to recover for 2 months, at which point the heart and intracardiac nerve plexus were isolated for electrophysiological and immunohistochemical analysis. Sham surgeries, in which the aorta was surgically visualized but undisturbed, were run in parallel. PO animals showed a significant increase in the size of the heart and lungs as a percent of body weight versus sham surgeries. Intracellular voltage recordings from parasympathetic postganglionic neurons showed no change in resting membrane properties in the sham or PO tissues versus age‐matched controls. However, neurons from PO hearts showed a significant increase in the magnitude of the histamine‐induced increase in neuronal excitability (as determined by the frequency of action potentials produced with depolarizing stimuli) as compared to both controls and sham surgeries. PO hearts also showed a three‐fold increase in the number of neuronal nitric oxide (nNOS) immunoreactive neurons (PO 15.2 + 1.8% versus controls 5.4 + 2.9%, p<0.02). These results indicate that chronic pressure overload induces a differential remodeling of intrinsic cardiac cellular phenotypes and functional up‐regulation of local network excitability. Supported by HL71830 (JLA) and R15 HL060619‐02 (JCH).

NK1 receptor activation by geniohyoid primary afferents modulates parasympathetic postganglionic neuronal excitability in the rat

Previous studies have indicated that the geniohyoid (GH) muscle receives innervation via both the hypoglossal nerve (CNXII) and the ansa cervicalis. Our recent studies revealed that the efferent root that contributes to the ansa cervicalis is a parasympathetic pathway and contains postganglionic cell bodies. Afferent axons from the GH muscle also travel via the ansa cervicalis, and afferent cell bodies are located in spinal ganglia. The present study attempts to locate the central terminations of these afferents. From the peripheral cut end of the ansa cervicalis, we recorded afferent discharges that coincided with inspiration and these were elicited by stretch of the GH muscle. After cutting CNXII proximal to its union with the ansa cervicalis, we applied horseradish peroxidase to the branch of CNXII that innervates the GH muscle. This procedure labeled cells ipsilaterally in the C2 spinal ganglia but not in the brainstem or upper spinal cord. Substance P-reactive terminals in the peripheral CNXII trunk were in apparent contact with vasoactive intestinal peptide-reactive cell bodies. Addition of the NK1 receptor agonist SP NK1 excited parasympathetic postganglionic neurons and the specific NK1 receptor antagonist GR82334 blocked these effects in vitro. These results suggest that GH primary afferents synapse on parasympathetic postganglionic neurons in the CNXII trunk and that activation of SP NK1 receptors modulates activity in these neurons.

Localization of Fibroblast Growth Factor-1 in Cholinergic Neurons Innervating the Rat Larynx

Cholinergic neurons in the dorsal motor nucleus of the vagus (DMNV) are particularly vulnerable to laryngeal nerve damage, possibly because they lack fibroblast growth factor-1 (FGF1). To test this hypothesis, we investigated the localization of FGF1 in cholinergic neurons innervating the rat larynx by immunohistochemistry using central-type antibodies to choline acetyltransferase (cChAT) and peripheral type (pChAT) antibodies, as well as tracer experiments. In the DMNV, only 9% of cChAT-positive neurons contained FGF1, and 71% of FGF1-positive neurons colocalized with cChAT. In the nucleus ambiguus, 100% of cChAT-positive neurons were FGF1 positive. In the intralaryngeal ganglia, all ganglionic neurons contained both pChAT and FGF1. In the nodose ganglia, 66% of pChAT-positive neurons were also positive for FGF1, and 90% of FGF1-positive ganglionic cells displayed pChAT immunoreactivity. Neuronal tracing using cholera toxin B subunit (CTb) demonstrated that cholinergic neurons sending their axons from the DMNV and nucleus ambiguus to the superior laryngeal nerve were FGF1 negative and FGF1 positive, respectively. In the nodose ganglia, some FGF1-positive cells were labeled with CTb. The results indicate that for innervation of the rat larynx, FGF1 is localized to motor neurons, postganglionic parasympathetic neurons, and sensory neurons, but expression is very low in preganglionic parasympathetic cholinergic neurons.

Unitary hypothesis for multiple triggers of the pain and strain of migraine

Migraine headache is triggered by and associated with a variety of hormonal, emotional, nutritional, and physiological changes. The perception of migraine headache is formed when nociceptive signals originating in the meninges are conveyed to the somatosensory cortex through the trigeminal ganglion, medullary dorsal horn, and thalamus. Is there a common descending pathway accounting for the activation of meningeal nociceptors by different migraine triggers? We propose that different migraine triggers activate a wide variety of brain areas that impinge on parasympathetic neurons innervating the meninges. According to this hypothesis, migraine triggers such as perfume, stress, or awakening activate multiple hypothalamic, limbic, and cortical areas, all of which contain neurons that project to the preganglionic parasympathetic neurons in the superior salivatory nucleus (SSN). The SSN, in turn, activates postganglionic parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation and local release of inflammatory molecules that activate meningeal nociceptors. Are there ascending pathways through which the trigeminovascular system can induce the wide variety of migraine symptoms? We propose that trigeminovascular projections from the medullary dorsal horn to selective areas in the midbrain, hypothalamus, amygdala, and basal forebrain are functionally positioned to produce migraine symptoms such as irritability, loss of appetite, fatigue, depression, or the quest for solitude. Bidirectional trafficking by which the trigeminovascular system can activate the same brain areas that have triggered its own activity in the first place provides an attractive network of perpetual feedback that drives a migraine attack for many hours and even days.