Central neuronal circuit innervating the rat heart defined by transneuronal transport of pseudorabies virus

We defined the central circuit innervating various regions of the rat heart using a neurotropic herpesvirus as a transneuronal tracer. Location of viral antigens in the brain after cardiac injection of three strains of pseudorabies virus (PRV) provided insight into vagal preganglionic neurons and their connected interneurons. At short survival times, labeled vagal preganglionic neurons were localized in both the nucleus ambiguus (NA) and the dorsal motor nucleus of the vagus (DMV), and in an arc-like band through the reticular formation between the NA and the DMV. The amount of DMV labeling was dependent on viral strain. Similar distributions of labeled neurons were observed following either ganglionic, sinoatrial node, or ventricular injections. At intermediate survival times postcardiac injection, the virus replicated in vagal preganglionic neurons and was trans- synaptically transported to interneurons observed primarily in the NA regions and in an arc-like band through the reticular formation. Labeled neurons were also observed in ventral regions of the nucleus of the solitary tract (NTS). At longer survival times, labeled neurons were found in various regions of the NTS with the most abundant label dorsal and dorsomedial to the solitary tract. Abundant neuronal labeling was also found in the intermediolateral cell column, the raphe nuclei, the caudal and rostral ventral lateral medulla, the A5 region, the locus coeruleus, and the lateral and paraventricular hypothalamic nuclei. These data define the central circuits including the interneuronal connections that innervate various cardiac targets.

[1]  J. Eccles,et al.  The action of a single vagal volley on the rhythm of the heart beat , 1934, The Journal of physiology.

[2]  A. Etemadi The dorsal motor nucleus of the vagus. , 1961, Acta anatomica.

[3]  F. Calaresu,et al.  Origin of cardiomotor fibres in the dorsal nucleus of the vagus in the cat: a historical study , 1965, The Journal of physiology.

[4]  Dunning Aj,et al.  Stimulation of the carotid sinus nerve , 1969 .

[5]  E. Braunwald,et al.  Parasympathetic control of the heart. , 1973, Pharmacological reviews.

[6]  J. Lipski,et al.  The sinus nerve and baroreceptor input to the medulla of the cat. , 1975, The Journal of physiology.

[7]  K. Spyer,et al.  The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. , 1976, The Journal of physiology.

[8]  Teiji Yamamoto,et al.  Origins of vagal preganglionic fibers to the sino-atrial and atrio-ventricular node regions in the cat heart as studied by the horseradish peroxidase method , 1977, Brain Research.

[9]  K. Spyer,et al.  The baroreceptor input to cardiac vagal motoneurones , 1978, The Journal of physiology.

[10]  R. Wurster,et al.  Cardiac Responses during Stimulation of the Dorsal Motor Nucleus and Nucleus Ambiguus in the Cat , 1980, Circulation research.

[11]  A. Loewy,et al.  Projections of the carotid sinus nerve to the nucleus of the solitary tract in the cat , 1980, Brain Research.

[12]  J. Ciriello,et al.  Distribution of vagal cardioinhibitory neurons in the medulla of the cat. , 1980, The American journal of physiology.

[13]  C. Polosa,et al.  Cardiovascular control by medullary surface chemoreceptors. , 1981, Journal of the autonomic nervous system.

[14]  J. W. Kozelka,et al.  Organization and reflex control of vagal cardiomotor neurons. , 1981, Journal of the autonomic nervous system.

[15]  C. Kidd,et al.  A horseradish peroxidase study of vagal motoneurones with axons in cardiac and pulmonary branches of the cat and dog. , 1981, Quarterly journal of experimental physiology.

[16]  S. Donoghue,et al.  Identification and brain‐stem projections of aortic baroreceptor afferent neurones in nodose ganglia of cats and rabbits. , 1982, The Journal of physiology.

[17]  S. Tamai,et al.  Vagal cardiac preganglionic neurons: distribution, cell types, and reflex discharges. , 1982, The American journal of physiology.

[18]  S. L. Stuesse Origins of cardiac vagal preganglionic fibers: A retrograde transport study , 1982, Brain Research.

[19]  D. van der Kooy,et al.  Organization of the projections of a circumventricular organ: The area postrema in the rat , 1983, The Journal of comparative neurology.

[20]  S. L. Stuesse,et al.  Projections to the cardioinhibitory region of the nucleus ambiguus of rat , 1984, The Journal of comparative neurology.

[21]  M. Lévy,et al.  Parasympathetic control of the heart , 1984 .

[22]  R. Shapiro,et al.  The central neural connections of the area postrema of the rat , 1985, The Journal of comparative neurology.

[23]  P. Luiten,et al.  The course of paraventricular hypothalamic efferents to autonomic structures in medulla and spinal cord , 1985, Brain Research.

[24]  A. Pappano,et al.  The parasympathetic neuroeffector junction of the heart. , 1985, Pharmacological reviews.

[25]  The aortic nerve-sympathetic reflex in the rat , 1985 .

[26]  D. Reis,et al.  Projections from the nucleus tractus solitarii to the rostral ventrolateral medulla , 1985, The Journal of comparative neurology.

[27]  J. Schwaber Neuroanatomical Substrates of Cardiovascular and Emotional — Autonomic Regulation , 1986 .

[28]  P. N. Mcwilliam,et al.  The effects of electrical stimulation of myelinated and non‐myelinated vagal fibres on heart rate in the rabbit. , 1986, The Journal of physiology.

[29]  Excitatory and inhibitory effects on respiration of l-glutamate microinjected superficially into the ventral aspects of the medulla oblongata in cat , 1987, Brain Research.

[30]  F. Abboud,et al.  Effects of pulse frequency on single‐unit baroreceptor activity during sine‐wave and natural pulses in dogs. , 1988, The Journal of physiology.

[31]  J. Coote The organisation of cardiovascular neurons in the spinal cord. , 1988, Reviews of physiology, biochemistry and pharmacology.

[32]  J C Smith,et al.  Brainstem projections to the major respiratory neuron populations in the medulla of the cat , 1989, The Journal of comparative neurology.

[33]  H. Rziha,et al.  Aujeszky’s Disease (Pseudorabies) in Pigs , 1989 .

[34]  A. Loewy,et al.  CNS cell groups regulating the sympathetic outflow to adrenal gland as revealed by transneuronal cell body labelling with pseudorabies virus , 1989, Brain Research.

[35]  J. Schwaber,et al.  Neurotropic properties of pseudorabies virus: uptake and transneuronal passage in the rat central nervous system , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[36]  L. Enquist,et al.  Two alpha-herpesvirus strains are transported differentially in the rodent visual system. , 1991, Neuron.

[37]  L. Enquist,et al.  Two α-herpesvirus strains are transported differentially in the rodent visual system , 1991, Neuron.

[38]  T. Mettenleiter Molecular biology of pseudorabies (Aujeszky's disease) virus. , 1991, Comparative immunology, microbiology and infectious diseases.

[39]  J S Schwaber,et al.  Tonically rhythmic neurons within a cardiorespiratory region of the nucleus tractus solitarii of the rat. , 1991, Journal of neurophysiology.

[40]  N. Bogan,et al.  Localization of cardiac parasympathetic preganglionic neurons in the medulla oblongata of pigeon, Columba livia: a study using fragment C of tetanus toxin , 1991, Brain Research.

[41]  L. Enquist,et al.  Pseudorabies virus envelope glycoprotein gI influences both neurotropism and virulence during infection of the rat visual system , 1992, Journal of virology.

[42]  G. Rakhorst,et al.  Transneuronal viral labelling of rat heart left ventricle controlling pathways. , 1993, Neuroreport.

[43]  A. Loewy,et al.  Specificity of pseudorabies virus as a retrograde marker of sympathetic preganglionic neurons: implications for transneuronal labeling studies , 1993, Brain Research.

[44]  J. Card,et al.  Spatiotemporal responses of astrocytes, ramified microglia, and brain macrophages to central neuronal infection with pseudorabies virus , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[45]  A. Robbins,et al.  Specific pseudorabies virus infection of the rat visual system requires both gI and gp63 glycoproteins , 1993, Journal of virology.

[46]  L. Rinaman,et al.  Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  J. Deuchars,et al.  Localization of cardiac vagal preganglionic motoneurones in the rat: Immunocytochemical evidence of synaptic inputs containing 5‐hydroxytryptamine , 1993, The Journal of comparative neurology.

[48]  L. Enquist,et al.  Innervation of the heart and its central medullary origin defined by viral tracing. , 1994, Science.

[49]  L. Enquist Infection of the mammalian nervous system by pseudorabies virus (PRV) , 1994 .