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

1 Department of Pharmacology and 3 Specialized Neuroscience Research Program, Howard University College of Medicine, Washington, District of Columbia 20059; and 2 Department of Pharmacology, East Tennessee State University, James H. Quillen College of Medicine, Johnson City, Tennessee 37614 Submitted 16 June 2003 ; accepted in final form 24 October 2003 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. intracardiac ganglia; retrograde transport; nucleus ambiguus; ultrastructure; posterior atrial ganglion Address for reprint requests and other correspondence: V. John Massari, Dept. of Pharmacology, Howard Univ. College of Medicine, 520 W St. N.W., Washington, DC 20059 (E-mail: vmassari{at}howard.edu ).