Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals

Massari, V. John; Dickerson, Linda W.; Gray, Alrich L.; Lauenstein, Jean-Marie; Blinder, Karen J.; Newsome, Joseph T.; Rodak, David J.; Fleming, Terry J.; Gatti, Philip J.; Gillis, Richard A.

doi:10.1016/s0006-8993(98)00613-1

Cited by 28 publications

(25 citation statements)

References 55 publications

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“…Similarly, studies in cats have suggested that the vagal cholinergic preganglionic neurons controlling negative chronotropic, dromotropic, and inotropic responses are distributed mainly in the nucleus ambiguus (45). However, in rats, a subpopulation of vagal preganglionic cell bodies within the external portion of the nucleus ambiguus that project to the heart do not express cholinergic traits (58).…”

Section: Discussionmentioning

confidence: 99%

“…The AVPNs do not express catechominergic traits, but tyrosine hydroxylase-positive axon terminals lie in their close proximity and, when stimulated, release norepinephrine within the rNA region causing withdrawal of cholinergic outflow to the airways (28). Similarly, in cats, tyrosine hydroxylase-immunoreactive terminals innervate nonadrenergic cardiac vagal preganglionic cells, commonly forming axodendritic synapses on these negative inotropic neurons (45).…”

Section: Discussionmentioning

confidence: 99%

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Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Mayer

Haxhiu

2004

Journal of Applied Physiology

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Kc, Prabha, Catherine A. Mayer, and Musa A. Haxhiu. Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons. J Appl Physiol 97: 1508 -1517, 2004; 10.1152/japplphysiol.00282.2004.-In ferrets, we investigated the presence of choline acetyltransferase (ChAT), vasoactive intestinal peptide (VIP), and markers for nitric oxide synthase (NOS) in preganglionic parasympathetic neurons innervating extrathoracic trachea and intrapulmonary airways. Cholera toxin ␤-subunit, a retrograde axonal transganglionic tracer, was used to identify airway-related vagal preganglionic neurons. Double-labeling immunohistochemistry and confocal microscopy were employed to characterize the chemical nature of identified airway-related vagal preganglionic neurons at a single cell level. Physiological experiments were performed to determine whether activation of the VIP and ChAT coexpressing vagal preganglionic neurons plays a role in relaxation of precontracted airway smooth muscle tone after muscarinic receptor blockade. The results showed that 1) all identified vagal preganglionic neurons innervating extrathoracic and intrapulmonary airways are acetylcholine-producing cells, 2) cholinergic neurons innervating the airways coexpress ChAT and VIP but do not contain NOS, and 3) chemical stimulation of the rostral nucleus ambiguus had no significant effect on precontracted airway smooth muscle tone after muscarinic receptor blockade. These studies indicate that vagal preganglionic neurons are cholinergic in nature and coexpress VIP but do not contain NOS; their stimulation increases cholinergic outflow, without activation of inhibitory nonadrenergic, noncholinergic ganglionic neurons, stimulation of which induces airway smooth muscle relaxation. Furthermore, these studies do not support the possibility of direct inhibitory innervation of airway smooth muscle by vagal preganglionic fibers that contain VIP.central nervous system control of the airways; parasympathetic preganglionic neurons; choline acetyl transferase; vasoactive intestinal peptide; nitric oxide synthase; nucleus ambiguus; airway constriction; airway dilation IN MANY SPECIES, INCLUDING HUMANS, airway smooth muscle (ASM) tone critically relies on the balance between central excitatory cholinergic control (3,19,33,49) and the inhibitory nonadrenergic, noncholinergic (iNANC) influences (2,12,17,47,56). Activation of cholinergic preganglionic neurons produces airway constriction, submucosal gland secretion and increased blood flow using acetylcholine as a neurotransmitter (23,25,26). In the presence of cholinergic and sympathetic blockade, stimulation of vagal nerves, either by electrical current or via neural reflex pathways, elicits relaxation of preconstricted ASM cells via activation of iNANC pathways (2,12,17,56). Recent studies indicate that the iNANC system employs vasoactive intestinal peptide (VIP) (7,16,22,38,47,57), nitric oxide (NO) (4, 30, 36, 44, 51), or both (6, 14 -16, 64) to elicit ASM relaxation. Ho...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Mayer

Haxhiu

2004

Journal of Applied Physiology

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“…Therefore, this anatomic evidence suggests that both nuclei could be important for cardiac function. Consistent with this morphological evidence, physiological data also support the functional significance of the two nuclei: 1) electrical stimulation of vagal efferent B fibers (presumably from NA) and vagal C fibers (presumably from DmnX) selectively evokes bradycardia, A-V block, and reduction of cardiac contractility (9,14,15,29); 2) stimulation of the DmnX elicits bradycardia and reduces myocardial contractility (4, 10, 24); 3) activation of the NA induces negative chronotropic, dromotropic, and inotropic effects (2,3,17,28); and 4) both DmnX and NA neurons are barosensitive (30). However, whether the two vagal motor nuclei perform different functional roles remains unclear.…”

mentioning

confidence: 88%

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence

Cheng

Zhang²,

Guo³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

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. Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence. Am J Physiol Regul Integr Comp Physiol 286: R625-R633, 2004. First published November 26, 2003 10.1152/ajpregu.00143. 2003.-In previous single-labeling experiments, we showed that neurons in the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX) project to intrinsic cardiac ganglia. Neurons in these two motor nuclei differ significantly in the size of their projection fields, axon caliber, and endings in cardiac ganglia. These differences in NA and DmnX axon cardiac projections raise the question as to whether they target the same, distinct, or overlapping populations of cardiac principal neurons. To address this issue, we examined vagal terminals in cardiac ganglia and tracer injection sites in the brain stem using two different anterograde tracers {1,1Ј-dioleyl-3,3,3Ј,3Ј-tetramethylindocarbocyanine methanesulfonate and 4-[4-(dihexadecylamino)-styryl]-N-methylpyridinium iodide} and confocal microscopy in male Sprague-Dawley rats. We found that 1) NA and DmnX neurons innervate the same cardiac ganglia, but these axons target separate subpopulations of principal neurons and 2) axons arising from neurons in the NA and DmnX in the contralateral sides of the brain stem enter the cardiac ganglionic plexus through separate bundles and preferentially innervate principal neurons near their entry regions, providing topographic mapping of vagal motor neurons in left and right brain stem vagal nuclei. Because the NA and DmnX project to distinct populations of cardiac principal neurons, we propose that they may play different roles in controlling cardiac function. brain stem; parasympathetic; anterograde tracing; heart; baroreflex VAGAL EFFERENT NERVE ACTIVATION induces negative chronotropic, dromotropic, and inotropic changes in the heart (13, 16). Our knowledge, however, of how the brain stem circuitry is organized to control the heart via the vagus is limited because of the complexity of brain-heart connections and limitations of previous anatomic techniques (8).Vagal efferent preganglionic axons arise mainly from neurons in two brain stem nuclei [the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DmnX)], whereas a small number of vagal efferent axons arise from neurons in the intermediate zone between DmnX and NA. The functional roles of cardiac neurons in these nuclei are not well understood (6,8,11,13,16,25). Furthermore, neurons in different cardiac ganglia control heart rate, arteriovenous (A-V) conduction, and myocardial contractility (17,18,(20)(21)(22). In contrast to the conventional concept that cardiac ganglia are simple relay stations for central nervous system input, these structures are more likely operating as complex integration centers (19, 23). They consist of sensory neurons, motor neurons, and interneurons that employ complex chemical coding (12,26) and are involved in local, as well as central, cardiac reflexes (1,19,23,27). Thus a major questi...

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“…Previous work has shown that tyrosine hydroxylase (TH, an essential enzyme in the generation of norepinephrine)-immunoreactive synapses innervate CVNs (Massari et al, 1998) and ␣ 1 -adrenergic receptors are also present within the NA (Day et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Optogenetic Stimulation of Locus Ceruleus Neurons Augments Inhibitory Transmission to Parasympathetic Cardiac Vagal Neurons via Activation of Brainstem α1 and β1 Receptors

et al. 2014

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Locus ceruleus (LC) noradrenergic neurons are critical in generating alertness. In addition to inducing cortical arousal, the LC also orchestrates changes in accompanying autonomic system function that compliments increased attention, such as during stress, excitation, and/or exposure to averse or novel stimuli. Although the association between arousal and increased heart rate is well accepted, the neurobiological link between the LC and parasympathetic neurons that control heart rate has not been identified. In this study, we test directly whether activation of noradrenergic neurons in the LC influences brainstem parasympathetic cardiac vagal neurons (CVNs). CVNs were identified in transgenic mice that express channel-rhodopsin-2 (ChR2) in LC tyrosine hydroxylase neurons. Photoactivation evoked a rapid depolarization, increased firing, and excitatory inward currents in ChR2-expressing neurons in the LC. Photostimulation of LC neurons did not alter excitatory currents, but increased inhibitory neurotransmission to CVNs. Optogenetic activation of LC neurons increased the frequency of isolated glycinergic IPSCs by 27 Ϯ 8% (p ϭ 0.003, n ϭ 26) and augmented GABAergic IPSCs in CVNs by 21 Ϯ 5% (p ϭ 0.001, n ϭ 26). Inhibiting ␣1, but not ␣2, receptors blocked the evoked responses. Inhibiting ␤1 receptors prevented the increase in glycinergic, but not GABAergic, IPSCs in CVNs. This study demonstrates LC noradrenergic neurons inhibit the brainstem CVNs that generate parasympathetic activity to the heart. This inhibition of CVNs would increase heart rate and risks associated with tachycardia. The receptors activated within this pathway, ␣1 and/or ␤1 receptors, are targets for clinically prescribed antagonists that promote slower, cardioprotective heart rates during heightened vigilant states.

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Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals

Cited by 28 publications

References 55 publications

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Chemical profile of vagal preganglionic motor cells innervating the airways in ferrets: the absence of noncholinergic neurons

Differential control over postganglionic neurons in rat cardiac ganglia by NA and DmnX neurons: anatomical evidence

Optogenetic Stimulation of Locus Ceruleus Neurons Augments Inhibitory Transmission to Parasympathetic Cardiac Vagal Neurons via Activation of Brainstem α1 and β1 Receptors

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