Autonomic innervation of the developing heart: Origins and function

Abstract

Maintenance of homeostatic circulation in mammals and birds is reliant upon autonomic innervation of the heart. Neural branches of mixed cellular origin and function innervate the heart at the arterial and venous poles as it matures, eventually coupling autonomic output to the cardiac components, including the conduction system. The development of neural identity is controlled by specific networks of genes and growth factors, whereas functional properties are governed by the use of different neurotransmitters. In this review, we summarize briefly the anatomic arrangement of the vertebrate autonomic nervous system and describe, in detail, the innervation of the heart. We discuss the timing of cardiac innervation in the chick and mouse, emphasizing the relationship of the cardiac neural networks to the anatomical structures within the heart. We also discuss the variable contribution of the neural crest to vagal cardiac nerves, and summarize the main neurotransmitters secreted by the developing sympathetic and parasympathetic autonomic divisions. We provide an overview of the main growth factor and gene families involved in neural development, discussing how these factors may impact upon the development of cardiac abnormalities in congenital syndromes associated with autonomic dysfunction.

Systematic and comparative morphologies of the extrinsic cardiac nervous system in lemurs (Primates: Strepsirrhini: Infraorder Lemuriformes, Gray, 1821) with evolutionary morphological implications

“…The parasympathetic vagal cardiac system and its cardiac branches are consistent among primates. Interestingly, the comparative anatomical findings of the variable sympathetic and constant parasympathetic ECNSs in primates are similar to the mammalian ontogeny of cardiac innervation; however, the sympathetic cardiac innervation has been shown to occur at later stages than the parasympathetic vagal cardiac innervation (Kirby et al, 1980;Shoba and Tay, 2000;Hildreth et al, 2009).…”

“…Experimental and developmental studies of the autonomic cardiac nervous system have also been conducted in animals such as the mouse, rat, rabbit, chick, and dog (Armour et al, 1972;Benítez et al, 1959;Brack et al, 2011;Gomez, 1958;Haws and Burgess, 1978;Hildreth et al, 2008Hildreth et al, , 2009Kirby et al, 1980;Kuratani et al, 1991;Kuratani and Tanaka, 1990;Levy et al, 1966;Mabe and Hoover, 2011;Meyer et al, 2010;Mizeres, 1955Mizeres, , 1957Mizeres, , 1958Mizuno et al, 2010;Oliveira et al, 2010;Roberts, 1991;Schwartz, 2010;Scherlag et al, 2011;Shaner, 1930;Shoba and Tay, 2000;Uchida et al, 2010;Verberne et al, 1998). However, huge differences in the cardiac nervous system between humans and the experimental animals have been recognized (Batulevicius et al, 2003;Brugnaro et al, 2003;Kawashima, 2011;McKibben and Getty, 1968;Rysevaite et al, 2011;Pauza et al, 2002a,b).…”

Comparative Anatomy and Evolution of the Cardiac Innervation in New World Monkeys (Platyrrhini, E. Geoffroy, 1812)

“…The mammalian and avian ontogenetic developmental studies of the ACNS are detailed in a number of papers (Kirby et al, 1980;Kuratani and Tanaka, 1990;Verberne et al, 1998;Shoba and Tay, 2000;Hildreth et al, 2008Hildreth et al, , 2009). In the chick, the innervation of the outflow tract (arterial porta) by the parasympathetic cardiac branches occurred between stages 28 and 29 of Humburger and Hamilton (HH), whereas the positive HNK1 staining is first observed at the 24th stage and reaches the venous sinus by the 26th stage, and further vagal cardiac branches develop (Kuratani and Tanaka, 1990;Verberne et al, 1998;Hildreth et al, 2009).…”

“…In the chick, the innervation of the outflow tract (arterial porta) by the parasympathetic cardiac branches occurred between stages 28 and 29 of Humburger and Hamilton (HH), whereas the positive HNK1 staining is first observed at the 24th stage and reaches the venous sinus by the 26th stage, and further vagal cardiac branches develop (Kuratani and Tanaka, 1990;Verberne et al, 1998;Hildreth et al, 2009). In the mouse, the parasympathetic vagal nerves are first seen in the venous porta at E10.5 (10.5 days after fertilization, equivalent to HH20 in the chick) and reach the heart by E12.5 (HH24), whereas the innervation of the outflow (arterial porta) occurs slightly later than seen in the chick (Hildreth et al, 2008).…”

The epicardium as modulator of the cardiac autonomic response during early development

“…Sympathetic neurons have their cell bodies primarily in the paravertebral stellate ganglion, whereas parasympathetic cell bodies are located in the cardiac ganglia [5]. The cells contributing to the cANS are derivatives of neural crest cells (NCCs) and cells of the nodose placode [6,7]. Kroese et al demonstrated that prior to cardiac sympathetic innervation of the developing chicken embryo, the heart already responds to the catecholamine epinephrine [8].…”