PERIAQUEDUCTAL GRAY-MATTER INPUT TO CARDIAC-RELATED SYMPATHETIC PREMOTOR NEURONS

The periaqueductal gray matter (PAG) serves as the midbrain link betwe en forebrain emotional processing systems and motor pathways used in t he defense reaction. Part of this response depends upon FAG efferent p athways that modulate cardiovascular-related sympathetic outflow syste ms, including those that regulate the heart. While it is known that th e FAG projects to vagal preganglionic neurons, including possibly card iovagal motoneurons, no information exists on the FAG circuits that ma y affect sympathetically mediated cardiac functions and, thus, the pur pose of this study was to use neuroanatomical methods to identify thes e 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 co ntained transynaptically infected neurons; these included the dorsomed ial, lateral and ventrolateral FAG columns as well as the Edinger-West phal and precommissural nuclei. Second, the descending efferent FAG pr ojections were studied with the anterograde axonal marker Phaseolus vu lgaris 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 sugges ting that the PAG modulates sympathetic functions by indirect pathways involving synaptic relays through sympathetic premotor cell groups, e specially those found in the medulla oblongata. This possibility was e xamined by a double tracing study. PHA-L was first injected into eithe r the lateral or ventrolateral FAG and after 6 days, PRV was injected into the ipsilateral stellate ganglion. After an additional 4 days sur vival, a double immunohistochemical procedure for co-visualization of PRV and PHA-L was used to identify the sympathetic premotor regions th at receive an input from the FAG. The FAG innervated specific groups o f sympathetic premotor neurons in the hypothalamus, pens, and medulla as well as providing reciprocal intercolumnar connections within the F AG itself (Jansen et al., Brain Res. 784 (1998) 329-336). The major ro ute terminates in the ventral medulla, especially within the medial re gion which contains sympathetic premotor neurons lying within the raph e magnus and gigantocellular reticular nucleus, pars alpha. Both serot onegic and non-serotonergic sympathetic premotor neurons in these two regions receive inputs from the FAG. Weak FAG projections to sympathet ic premotor neurons were found in the rostral ventrolateral medulla (i ncluding to Cl adrenergic neurons), locus coeruleus, A5 cell group, pa raventricular and lateral hypothalamic nuclei. In summary, both the la teral and ventrolateral FAG columns appear to be capable of modulating cardiac sympathetic functions via a series of indirect pathways invol ving sympathetic premotor neurons found in selected sites in the hypot halamus, midbrain, pens, and medulla oblongata, with the major outflow terminating in bulbospinal regions of the rostral ventromedial medull a. (C) 1998 Elsevier Science B.V.