Parasympathetic control of the heart. III. Neuropeptide Y-immunoreactive nerve terminals synapse on three populations of negative chronotropic vagal preganglionic neurons

2004 ◽  
Vol 96 (6) ◽  
pp. 2279-2287 ◽  
Author(s):  
Alrich L. Gray ◽  
Tannis A. Johnson ◽  
Jean-Marie Lauenstein ◽  
Stephen S. Newton ◽  
Jeffrey L. Ardell ◽  
...  

The vagal postganglionic control of cardiac rate is mediated by two intracardiac ganglia, i.e., the sinoatrial (SA) and posterior atrial (PA) ganglia. Nothing is known about the vagal preganglionic neurons (VPNs) that innervate the PA ganglion or about the neurochemical anatomy of central afferents that innervate these VPNs. These issues were examined using light microscopic retrograde labeling methods and dual-labeling electron microscopic histochemical and immunocytochemical methods. VPNs projecting to the PA ganglion are found in a narrow column exclusively in the ventrolateral nucleus ambiguus (NA-VL). These neurons are relatively large (37.6 ± 2.7 μm by 21.3 ± 3.4 μm) with abundant cytoplasm and intracellular organelles, rare somatic and dendritic spines, round uninvaginated nuclei, and myelinated axons. Previous physiological data indicated that microinjections of neuropeptide Y (NPY) into the NA-VL cause negative chronotropic effects. The present morphological data demonstrate that NPY-immunoreactive nerve terminals formed 18 ± 4% of the axodendritic or axosomatic synapses and close appositions on VPNs projecting to the PA ganglion. Three approximately equal populations of VPNs in the NA-VL were retrogradely labeled from the SA and PA ganglia. One population each projects to the SA ganglion, the PA ganglion, or to both the SA and PA ganglia. Therefore, there are both shared and independent pathways involved in the vagal preganglionic controls of cardiac rate. These data are consistent with the hypothesis that the central and peripheral parasympathetic controls of cardiac rate are coordinated by multiple potentially redundant and/or interacting pathways and mechanisms.

2004 ◽  
Vol 96 (1) ◽  
pp. 260-270 ◽  
Author(s):  
Constance T. Moore ◽  
Christopher G. Wilson ◽  
Catherine A. Mayer ◽  
Sandra S. Acquah ◽  
V. John Massari ◽  
...  

GABA is the main inhibitory neurotransmitter that participates in the regulation of cholinergic outflow to the airways. We have tested the hypothesis that a monosynaptic GABAergic circuit modulates the output of airway-related vagal preganglionic neurons (AVPNs) in the rostral nucleus ambiguus by using a dual-labeling electron microscopic method combining immunocytochemistry for glutamic acid decarboxylase (GAD) with retrograde tracing from the trachea. We also determined the effects of blockade of GABAA receptors on airway smooth muscle tone. The results showed that retrogradely labeled AVPNs received a significant GAD-immunoreactive (GAD-IR) terminal input. Out of a pooled total of 3,161 synaptic contacts with retrogradely labeled somatic and dendritic profiles, 20.2% were GAD-IR. GAD-IR terminals formed significantly more axosomatic synapses than axodendritic synapses ( P < 0.02). A dense population of GABAergic synaptic contacts on AVPNs provides a morphological basis for potent physiological effects of GABA on the excitability of AVPNs. GAD-IR terminals formed exclusively symmetric synaptic specializations. GAD-IR terminals were significantly larger ( P < 0.05) in both length and width than unlabeled terminals synapsing on AVPNs. Therefore, the structural characteristics of certain nerve terminals may be closely correlated with their function. Pharmacological blockade of GABAA receptors within the rostral nucleus ambiguus increased activity of putative AVPNs and airway smooth muscle tone. We conclude that a tonically active monosynaptic GABAergic circuit utilizing symmetric synapses regulates the discharge of AVPNs.


1990 ◽  
Vol 259 (5) ◽  
pp. R955-R962
Author(s):  
B. H. Machado ◽  
M. J. Brody

We showed previously that activation of nucleus ambiguus (NA) induced bradycardia and increased arterial pressure. In this study, we compared responses produced by electrical and chemical (glutamate) stimulation of NA and adjacent rostral ventrolateral medulla (RVLM). Equivalent pressor responses were elicited from both areas. However: 1) The response from RVLM was elicited at a lower frequency. 2) Regional vascular resistance changes were different, i.e., electrical stimulation of NA increased vascular resistance in hindquarters much more than the renal and mesenteric beds. In contrast, electrical and chemical stimulation of RVLM produced a more prominent effect on the renal vascular bed. 3) Bradycardia was elicited from NA at lower current intensity. 4) Glutamate produced bradycardia only when injected into NA. Studies in rats with sinoaortic deafferentation showed that bradycardic response to activation of NA was only partly reflex in origin. We conclude that 1) NA and RVLM control sympathetic outflow to regional vascular beds differentially and 2) the NA region involves parasympathetic control of heart rate and sympathetic control of arterial pressure.


1991 ◽  
Vol 261 (3) ◽  
pp. H969-H973 ◽  
Author(s):  
L. S. Sun ◽  
P. C. Ursell ◽  
R. B. Robinson

The onset of sympathetic innervation induces a developmental change in the cardiac alpha 1-adrenergic chronotropic response from an increase to a decrease in rate. The mechanism by which innervation induces this alteration is unknown. Neuropeptide Y (NPY), which is found abundantly in cardiac sympathetic nerve terminals, was considered as a possible mediator for this effect. Chronic conditioning by NPY in noninnervated myocyte cultures stimulated the effect of sympathetic innervation in inducing the alpha 1-inhibitory chronotropic response. Chronic conditioning by the NPY antagonist PYX-2 blocked the effect of innervation. Thus endogenous NPY may modulate alpha 1-adrenergic responsiveness during the ontogeny of cardiac sympathetic innervation.


1986 ◽  
Vol 102 (3) ◽  
pp. 716-730 ◽  
Author(s):  
J Covault ◽  
J R Sanes

Previous studies of denervated and cultured muscle have shown that the expression of the neural cell adhesion molecule (N-CAM) in muscle is regulated by the muscle's state of innervation and that N-CAM might mediate some developmentally important nerve-muscle interactions. As a first step in learning whether N-CAM might regulate or be regulated by nerve-muscle interactions during normal development, we have used light and electron microscopic immunohistochemical methods to study its distribution in embryonic, perinatal, and adult rat muscle. In embryonic muscle, N-CAM is uniformly present on the surface of myotubes and in intramuscular nerves; N-CAM is also present on myoblasts, both in vivo and in cultures of embryonic muscle. N-CAM is lost from the nerves as myelination proceeds, and from myotubes as they mature. The loss of N-CAM from extrasynaptic portions of the myotube is a complex process, comprising a rapid rearrangement as secondary myotubes form, a phase of decline late in embryogenesis, a transient reappearance perinatally, and a more gradual disappearance during the first two postnatal weeks. Throughout embryonic and perinatal life, N-CAM is present at similar levels in synaptic and extrasynaptic regions of the myotube surface. However, N-CAM becomes concentrated in synaptic regions postnatally: it is present in postsynaptic and perisynaptic areas of the muscle fiber, both on the surface and intracellularly (in T-tubules), but undetectable in portions of muscle fibers distant from synapses. In addition, N-CAM is present on the surfaces of motor nerve terminals and of Schwann cells that cap nerve terminals, but absent from myelinated portions of motor axons and from myelinating Schwann cells. Thus, in the adult, N-CAM is present in synaptic but not extrasynaptic portions of all three cell types that comprise the neuromuscular junction. The times and places at which N-CAM appears are consistent with its playing several distinct roles in myogenesis, synaptogenesis, and synaptic maintenance, including alignment of secondary along primary myotubes, early interactions of axons with myotubes, and adhesion of Schwann cells to nerve terminals.


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