Selective vagal innervation of the heart

Parasympathetic ganglia are imbedded (1) in the epicardial fat pad located on the posterior surface of the dog's heart and (2) immediately overlying the point of penetration by the coronary sinus into the interatrial septum. The fat pad is situated between the inferior vena cava and the inferior left atrium. It contains multiple encapsulated ganglia, each consisting of two to 80 separate cells, richly intermingled with neural elements. Destruction of these ganglia by surgical excision and/or phenol painting interrupts both right and left vagal inhibition of atrio-ventricular (A-V) conduction, without obviously altering vagal modulation of sinoatrial function. Excision or phenol destruction of the fat pad overlying the right pulmonary vein inlets to the left atrium interrupts both right and left vagal inhibition of sinoatrial function, again without interfering with vagal control of atrioventricular nodal function. Well organized, encapsulated autonomic ganglia are also found throughout this fat pad. These experiments thus identify and localize separate concentrations of ganglion cells which differentially modulate automaticity and A-V conduction in the canine heart.     

Segmental motor innervation of the cat diaphragm

In ten anaesthetized adult cats, bipolar recording electrodes were inserted in different muscular bundles of each hemi-diaphragm. Both stimulation and section of the phrenic cervical branches were made. The upper phrenic cervical branch innervates both the sternal and lateral portions of the diaphragm whereas the lower phrenic cervical branch innervates both the lateral and dorso-caudal portions.     

The development of vagal innervation of the bovine stomach

The development of the vagal innervation of the bovine stomach was examined in serial section from 15 embryos ranging from 10 to 20 mm crown-rump length. Models of the gastric epithelium and nerves were made of an 11, 14, and 20 mm embryo. The vagal innervation of the stomach was also examined in six bovine fetuses ranging from 15 to 52 cm in length. The bovine stomach developed from a spindle-shaped primordium at 10 mm to a four-chambered organ at 20 mm. At 11 mm, the right and left vagus extended to a point dorsal to the heart where they divided into dorsal and ventral branches. The ventral branches fused to form the ventral vagal trunk and the dorsal branches fused to form the dorsal vagal trunk. At the 12 to 14 mm stage, both vagal trunks ran along the lesser curvature of the gastric pri-mordium to the level of the developing abomasum. By 20 mm, the principal branches of the vagal trunks found in the adult were established and it became clear that the dorsal and ventral vagal trunks innervated areas of the ruminant stomach roughly comparable to the visceral and parietal (posterior and anterior (NA)) surfaces, respectively, of the simple stomach. The distribution of the vagal trunks in the fetuses was similar to that in the adult. Similarities in the development of the gastric nerves in man and ox were discussed.     

Dissociation between nerve-muscle transmission and nerve trophic effects on rat diaphragm using type D botulinum toxin.

Small doses of botulinum toxin can produce partial blockage of transmitter release at the nerve--muscle junction. 2. Subthreshold e.p.p.s, 3--10 days after poisoning, show a distribution of amplitudes that is fitted by Poisson statistics. Successive e.p.p.s. in a short train show a marked facilitation. 3. Two weeks or more after poisoning with a dose of toxin that paralyses the whole muscle, when nerve--muscle transmission is in course of recovery, subthreshold e.p.p.s have an amplitude distribution that is fitted by binomial statistics. This property of transmission is similar to those described in newly formed nerve--muscle junctions, during embryogenesis or regeneration. 4. Muscle fibres with subthreshold transmission in the 5--10 day group of muscles were all supersensitive to ACh, as were a number of fibres in which nerve stimulation still produced an action potential. 5. Two weeks or more after poisoning, muscle fibres with subthreshold transmission had lost their extrajunctional ACh-sensitivity, as had many fibres with m.e.p.p.s of roughly normal frequency but no response to nerve stimulation. 6. In diaphragm muscles poisoned with botulinum toxin between 1 and 4 days previously, the rate of fast axonal transport of radioactively labelled proteins down the phrenic nerve is not greatly affected, but the amount of materials carried is reduced to about one quarter of normal. These labelled proteins accumulate in the intramuscular portion of the phrenic nerve, in or near the nerve terminals, to a much greater extent than in controls, showing that the normal release of some of these materials has been prevented by the toxin. 7. It is concluded that the blockage of the trophic effects of nerves by botulinum toxin is due to a blockage of release of trophic factors other than ACh. 8. The muscle nerve cannot maintain a muscle in its normal state simply by activation of contraction, and a regenerating nerve terminal can restore a muscle towards its normal state before it can release enough ACh to produce muscle contraction.     

5-Hydroxytryptamine participation in the vagal inhibitory innervation of the stomach

1. Intraluminal pressure was recorded from the isolated guinea-pig and mouse stomach with the vagus and sympathetic nerves attached.2. The response to vagal stimulation, which consists of an excitatory and an inhibitory component, resembled the response to 5-hydroxytryptamine (5-HT), which has no direct action on the muscle but acts on intrinsic excitatory and inhibitory ganglia.3. In the presence of hyoscine, the effect of vagal stimulation, of nicotinic compounds and of 5-HT were all purely relaxant. Competitive block of ganglionic receptors for acetylcholine reduced the vagal relaxation without antagonizing 5-HT. Specific desensitization of ganglionic receptors for 5-HT reduced the vagal relaxation without antagonizing nicotinic compounds.4. During the early phase of the blocking action of nicotine, responses to vagal stimulation and to 5-HT were both abolished. As the non-specific antagonism changed to the later phase of specific antagonism to acetylcholine, the inhibitory (but not the excitatory) component of the vagal response recovered partially, in parallel with the recovery of the relaxant effect of 5-HT.5. The vagal inhibitory effect was completely abolished only when competitive block of acetylcholine receptors was combined with desensitization of 5-HT receptors.6. Stimulation of the mouse stomach (after asphyxiation of the mucosa and exclusion of the luminal content) in the presence of hyoscine caused the release of 5-HT; this release was blocked by tetrodotoxin.7. The results, together with previous observations that 5-HT is contained within preganglionic nerve fibres in the myenteric plexus, are consistent with the hypothesis that 5-HT, with acetylcholine, may be a neurotransmitter in the vagal inhibitory innervation of the stomach.     

Contribution to the study of diaphragm innervation in Nelore bovines

The phrenic nerves, in Nelore bovines, divide more frequently (60%) in a dorsal branch and a ventrolateral trunk, in both left and right sides. Another division, in trifurcation, giving off dorsal, lateral and ventral branches occurred in 23.3% of cases in the right side and in 30% left side. The division in ventral branch and dorsolateral trunk was observed in 16.6% of cases in the right side and 10% left side. The dorsal branches, both left and right, were distributed among their corresponding lumbar portions in all the cases verified. In 3% of the muscles studied, the right dorsal branch sent a nervous twig to caudal vena cava, and in 73.3% of the muscles, the left dorsal branch innervated the left lumbar portion and also sent some twigs which, after crossing the middle line, distributed in the right lumbar portion, ventral to esophageal hiatus. The lateral and ventral branches, in both left and right sides, innervated corresponding parts of the muscle. Connections (anastomosis) were observed between left lateral and dorsal branches in 10% of cases, and between dorsal left and right branches in 6.7% of cases.     

Hypothesis that vagal reinervation of diaphragm could sensitise it to electrical stimulation

The hypothesis proposed is that restoration of functional capacity of denervated diaphragm may be achieved by reinervating it with vagus nerve. Following trauma, carcinomatose infiltration, and/or large thoracic surgery and neck surgery, phrenic nerve is frequently injured. Reinervation even in the most favourable conditions would not follow and diaphragm would rest permanently denervated and paralysed. This results in unilateral or bilateral paralysis of diaphragm. In principle, intermittent electrical stimulation of the phrenic nerve or diaphragm could elicit regular diaphragm contractions and maintain satisfactory respiration. While this technique could be used in upper motor neurone injury, in lower motor neurone injury and denervated diaphragm, that imposes too high electrical resistance, direct diaphragm pacing is practically impossible. In these cases, long term artificial ventilation is often necessary. Nevertheless, those patients are at high risk to suffer from atelectasis and respiratory infections. We project a hypothesis that reinervation of denervated diaphragm by vagus nerve could re-establishes its sensitivity to intramuscular electrical stimulation and may allow stimulation of the diaphragm by implanted pace-maker electrodes. An appropriate electrical stimulation might then be possible and diaphragm pacing could replace prolonged artificial ventilation in those patients. Restoration of functional capacity of denervated diaphragm could open a perspective for long term diaphragm pacing in patients with irreversible phrenic nerve injury and diaphragm paralysis.     

Organizational effects of oxytocin on serotonin innervation

Oxytocin (OT) has an organizational effect within the central nervous system and can have long‐lasting effects on the expression of social behavior. OT has recently been implicated in modulating the release of serotonin through activation of receptors in the raphe nuclei. Here we test the hypothesis that OT can have an organizational effect on the serotonergic system. Male prairie voles received an intraperitoneal injection on postnatal day 1 with 3.0 or .3 µg OT, an OT antagonist, or a saline control. Brains were collected on day 21 and immunostained for serotonin. Serotonin axons were quantified in the anterior hypothalamus, cortical amygdala, medial amygdala, paraventricular nucleus of the hypothalamus, and ventromedial hypothalamus. Males treated with 3.0 µg OT displayed significantly higher serotonin axon length densities in the anterior hypothalamus, cortical amygdala, and the ventromedial hypothalamus than control males. These results support the hypothesis that OT has an organizational effect on the serotonin system during the neonatal period, and that these effects are site‐specific. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 54:92–97, 2012.     

Acute effects of capsaicin on gastrointestinal vagal afferents

Capsaicin is an important tool for investigation of thin afferent fibres, but its acute effects on subtypes of vagal afferent endings are unknown. In the gastrointestinal tract, these subtypes are: muscle endings (thought to be purely tension sensitive), mucosal endings (sensitive to stroking and chemical stimuli) and endings in the oesophagus with both properties. Acute capsaicin sensitivity was investigated in ferrets using in vivo and in vitro methods. Single-fibre activity was recorded from 63 vagal afferents: 12 Adelta-fibres, 15 C-fibres and 36 unclassified fibres with endings in the oesophagus (n=42), stomach (n=19) and duodenum (n=2). Responses to capsaicin occurred independently of motility changes and were therefore due to direct activation of the receptor ending. In the oesophagus in vivo, two of 10 tension receptors and one of one mucosal receptor responded to intraluminal application of 3.25 mM capsaicin. In the stomach and duodenum, five of 14 tension receptors and two of four mucosal receptors responded to close-systemic (32-164 nmol) capsaicin. In an in vitro gastro-oesophageal preparation, three of five tension, four of 21 mucosal and two of eight tension/mucosal receptors responded to topical application of 1mM capsaicin. Occurrence of responses was therefore unrelated to location of endings and isolation of tissue. Responsiveness was also unrelated to conduction velocity. Capsaicin caused desensitization of responses to further capsaicin application in 37% of afferents. It additionally caused cross-desensitization to mechanical stimuli, which was also seen in afferents that did not respond directly to capsaicin.In conclusion, capsaicin acutely activates all subtypes of gut vagal afferents in vivo and in vitro, although responsiveness is restricted to 30% of fibres and follows no specific pattern. Acute desensitization may be induced with or without a response.