Postnatal development of the rat intrinsic cardiac nervous system: a confocal laser scanning microscopy study in whole-mount atria

Horackova, Magda; Slavikova, Jana; Byczko, Zenobia

doi:10.1054/tice.2000.0126

Cited by 35 publications

(24 citation statements)

References 23 publications

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“…A variety of neurotransmitters and neuromodulators, including PACAP and VIP, appear to be involved in the relaying of information within intracardiac ganglia and onto effector targets such as cardiac valves, coronary arteries, and cardiomyocytes. PACAP and VIP have been detected by immunocytochemistry in nerve fibers in the heart, coronary vasculature, and cardiac parasympathetic ganglia (15)(16)(17)(18)(19)(20). Although extrinsic fibers may be one source of these neuropeptides in the heart (21), PACAP and VIP are also found in cell bodies and nerve fibers of intrinsic cardiac neurons (15)(16)(17)(18)(19)(20).…”

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confidence: 99%

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

DeHaven

Cuevas

2004

Journal of Biological Chemistry

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have been found within mammalian intracardiac ganglia, but the cellular effects of these neuropeptides remain poorly understood. Fluorometric calcium imaging and whole cell patch clamp recordings were used to examine the effects of PACAP and VIP on [ Pituitary adenylate cyclase-activating polypeptide (PACAP) 1 and vasoactive intestinal polypeptide (VIP) are pleiotropic neuropeptides that belong to the glucagon/secretin/growth hormone-releasing factor family of peptides (1-4). These neuropeptides have pronounced effects on the central nervous system as well as on neurons and effector targets of the autonomic nervous system. For example, in the central nervous system, PACAP is involved in hippocampal synaptic plasticity and associative learning in mice (5), whereas VIP has been shown to regulate intrathalamic rhythm activity and may modulate information transfer through the thalamocortical circuit (6). In the peripheral nervous system, PACAP and VIP appear to play a major role in autonomic regulation of the cardiovascular system. VIP has been shown to cause positive chronotropic and inotropic effects (7-9). In contrast, PACAP has been shown to cause a transient increase in sinus rate and atrial contractility that is followed by negative chronotropic and inotropic responses in isolated canine atria (10). Also, both PACAP and VIP are potent dilators of coronary arteries (11,12). Whereas these neuropeptides can directly influence cardiac tissues, the effects of PACAP and VIP on the heart are in part due to neuroregulatory effects on parasympathetic intracardiac ganglia (9,10,13,14).Mammalian intracardiac ganglia play a major role in neuronal control of the heart and are believed to be capable of independently monitoring and influencing cardiac function. A variety of neurotransmitters and neuromodulators, including PACAP and VIP, appear to be involved in the relaying of information within intracardiac ganglia and onto effector targets such as cardiac valves, coronary arteries, and cardiomyocytes. PACAP and VIP have been detected by immunocytochemistry in nerve fibers in the heart, coronary vasculature, and cardiac parasympathetic ganglia (15)(16)(17)(18)(19)(20). Although extrinsic fibers may be one source of these neuropeptides in the heart (21), PACAP and VIP are also found in cell bodies and nerve fibers of intrinsic cardiac neurons (15)(16)(17)(18)(19)(20). Despite the fact that data clearly demonstrate that these endogenous neuropeptides are potent regulators of the cardiovascular system, the cellular mechanisms mediating their effects remain poorly understood. There are also conflicting reports in the literature concerning the mechanisms by which PACAP and VIP regulate the function of intrinsic cardiac neurons. For example, it has been suggested that PACAP and VIP modulate neurotransmission

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confidence: 99%

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

DeHaven

Cuevas

2004

Journal of Biological Chemistry

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“…Although global cardiac sympathetic innervation was diminished in cKOs, the TH-positive intrinsic cardiac ganglia exhibited decreased neurite outgrowth and TH expression. This emphasizes that these structures are subject to the influences of SHP-2 and pERK signaling and, in the context of sinus bradycardia, reinforces their functional role in the heart brain and the idea that they are involved in heart rate regulation particularly in the first 2-3 wk of life (22,23,25,26). The dearth of axonal projections emanating from these ganglia combined with the loss of sympathetic-specific TH expression despite continued expression of the generic neuronal marker NSβT suggests that failure of sympathetic neurons to differentiate or to maintain their differentiated state may be the underlying mechanism for the altered sympathetic innervation in mutant hearts.…”

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confidence: 64%

“…Sympathetic (i.e., TH-positive) innervation is first observed at the base of the fetal heart; this innervation then extends onto the surface of the atria and eventually to the ventricles before following blood vessels into the ventricular wall to innervate the myocardium and project to the sinoatrial and atrioventricular nodes postnatally (27). The sympathetic innervation of the heart is not functionally relevant (i.e., does not control heart rate) until the second postnatal week of life in rodents (23,28,29), and the adult pattern of innervation is not fully achieved until 3 wk after birth (23,30). This developmental process requires nerve growth factor (NGF), which is produced by the target organ (the myocardium in the case of the heart) and is the main neurotrophic factor in establishing and maintaining sympathetic innervation (31).…”

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confidence: 99%

“…From there, a subset of sympathetic NC cells undergoes a second migration to the cervicothoracic and intrinsic cardiac ganglia to establish populations of sympathetic neurons which contribute to the cardiac plexus or "heart brain" (5,20,21). Recent studies exploring the extensive complexity of autonomic cardiac innervation revealed multiple levels of regulation and interaction between parasympathetic and sympathetic arms of autonomic innervation that converges in the heart brain to control cardiac function (20)(21)(22)(23)(24)(25)(26). Sympathetic (i.e., TH-positive) innervation is first observed at the base of the fetal heart; this innervation then extends onto the surface of the atria and eventually to the ventricles before following blood vessels into the ventricular wall to innervate the myocardium and project to the sinoatrial and atrioventricular nodes postnatally (27).…”

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confidence: 99%

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SHP-2 deletion in postmigratory neural crest cells results in impaired cardiac sympathetic innervation

Lajiness

Snider

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Autonomic innervation is an essential component of cardiovascular regulation that is first established from the neural crest (NC) lineage in utero and continues developing postnatally. Although in vitro studies have indicated that SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a signaling factor critical for regulating sympathetic neuron differentiation, this has yet to be shown in the complex in vivo environment of cardiac autonomic innervation. Targeting SHP-2 within postmigratory NC lineages resulted in a fully penetrant mouse model of diminished sympathetic cardiac innervation and concomitant bradycardia. Immunohistochemistry of the sympathetic nerve marker tyrosine hydroxylase revealed a progressive loss of adrenergic ganglionic neurons and reduction of cardiac sympathetic axon density in Shp2 cKOs. Molecularly, Shp2 cKOs exhibit lineage-specific suppression of activated phospo-ERK1/2 signaling but not of other downstream targets of SHP-2 such as pAKT. Genetic restoration of the phosphorylated-extracellular signalregulated kinase (pERK) deficiency via lineage-specific expression of constitutively active MEK1 was sufficient to rescue the sympathetic innervation deficit and its physiological consequences. These data indicate that SHP-2 signaling specifically through pERK in postmigratory NC lineages is essential for development and maintenance of sympathetic cardiac innervation postnatally.A lthough autonomic innervation of the heart begins in utero, functional neurocardiac coupling continues postnatally. Autonomic imbalance and irregular cardiac innervation density result in deadly consequences such as cardiac arrhythmias, heart failure, and sudden cardiac death (1-4). Although a balance between the sympathetic and parasympathetic arms of the autonomic nervous system is required to regulate heart rate, conduction velocity, and the force of each contraction, sympathetic tone predominates in determining the basal heart rate in the mouse.The sympathetic nervous system arises from the neural crest (NC) lineage. Trunk NC cells delaminate and migrate ventrally through the somites to establish the sympathetic trunk ganglia near the dorsal aorta (5, 6). Postmigration, cross-regulatory transcription factors such as Mash1, Phox2a and 2b, and Gata3 (7-13) are temporarily expressed and drive these NC cells to acquire a neuronal fate and eventually to differentiate into sympathetic neurons expressing both neuron specific β-tubulin (NSβT) and tyrosine hydroxylase (TH; the rate-limiting enzyme in catecholamine synthesis) (14-19). From there, a subset of sympathetic NC cells undergoes a second migration to the cervicothoracic and intrinsic cardiac ganglia to establish populations of sympathetic neurons which contribute to the cardiac plexus or "heart brain" (5,20,21). Recent studies exploring the extensive complexity of autonomic cardiac innervation revealed multiple levels of regulation and interaction between parasympathetic and sympathetic arms of autonomic innervation that converges in the heart brain to contr...

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“…The development of small vessel myography techniques, both wire and perfusion, when coupled to light microscopy provided a simple, easy to use and reliable measure of wall to lumen dimensions which revolutionised the in-vitro studies of resistance vessels [15,16]. More recently, the cellular aspects of vascular changes have been examined using laser scanning confocal microscopy which has the potential to provide valuable new information on vascular wall morphological processes, however, this technique remains expensive and is unavailable to most laboratories [17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%