Periaqueductal gray matter input to cardiac-related sympathetic premotor neurons

The periaqueductal gray matter (PAG) serves as the midbrain link between forebrain emotional processing systems and motor pathways used in the defense reaction. Part of this response depends upon FAG efferent pathways that modulate cardiovascular-related sympathetic outflow systems, including those that regulate the heart. While it is known that the FAG projects to vagal preganglionic neurons, including possibly cardiovagal motoneurons, no information exists on the FAG circuits that may affect sympathetically mediated cardiac functions and, thus, the purpose of this study was to use neuroanatomical methods to identify these pathways. First, viral transneuronal retrograde tracing experiments were performed in which pseudorabies virus (PRV) was injected into the stellate ganglion of rats. After 4 days survival, five FAG regions contained transynaptically infected neurons; these included the dorsomedial, lateral and ventrolateral FAG columns as well as the Edinger-Westphal and precommissural nuclei. Second, the descending efferent FAG projections were studied with the anterograde axonal marker Phaseolus vulgaris leuco-agglutinin (PHA-L) with a particular focus on determining whether the FAG projects to the intermediolateral cell column (IML). Almost no axonal labeling was found throughout the thoracic IML suggesting that the PAG modulates sympathetic functions by indirect pathways involving synaptic relays through sympathetic premotor cell groups, especially those found in the medulla oblongata. This possibility was examined by a double tracing study. PHA-L was first injected into either the lateral or ventrolateral FAG and after 6 days, PRV was injected into the ipsilateral stellate ganglion. After an additional 4 days survival, a double immunohistochemical procedure for co-visualization of PRV and PHA-L was used to identify the sympathetic premotor regions that receive an input from the FAG. The FAG innervated specific groups of sympathetic premotor neurons in the hypothalamus, pens, and medulla as well as providing reciprocal intercolumnar connections within the FAG itself (Jansen et al., Brain Res. 784 (1998) 329-336). The major route terminates in the ventral medulla, especially within the medial region which contains sympathetic premotor neurons lying within the raphe magnus and gigantocellular reticular nucleus, pars alpha. Both serotonegic and non-serotonergic sympathetic premotor neurons in these two regions receive inputs from the FAG. Weak FAG projections to sympathetic premotor neurons were found in the rostral ventrolateral medulla (including to Cl adrenergic neurons), locus coeruleus, A5 cell group, paraventricular and lateral hypothalamic nuclei. In summary, both the lateral and ventrolateral FAG columns appear to be capable of modulating cardiac sympathetic functions via a series of indirect pathways involving sympathetic premotor neurons found in selected sites in the hypothalamus, midbrain, pens, and medulla oblongata, with the major outflow terminating in bulbospinal regions of the rostral ventromedial medulla. (C) 1998 Elsevier Science B.V.