Integration in the ventral medulla and coordination of sympathetic, pain and arousal functions

The nucleus paragigantocellularis lateralis (PGi) in the rostral ventral medulla is implicated in several functions including cardiovascular control, respiration, pain and analgesia. More recent studies implicate this region in alertness and attention as well, by virtue of its prominent projections to the nucleus locus coeruleus (LC). To investigate information that is integrated in the PGi, we used tract tracing to examine brain and spinal projections to this region. Afferents to PGi were found to be functionally diverse and topographically organized. Projections to the retrofacial PGi are primarily autonomic in nature. A wider range of inputs were found to target the rostral (juxtafacial) aspect of the PGi, including brain nuclei involved in the processing of somatosensory and auditory stimuli, as well as autonomic areas. Efferent projections to the LC were also examined in detail. Neuropharmacology experiments revealed that the PGi provides a potent excitatory amino acid input to the LC and an inhibitory input acting at alpha 2 receptors on LC neurons. PGi neurons projecting to the LC stained for markers of adrenaline, enkephalin, GABA and corticotropin releasing factor. Finally, some PGi neurons collateralize to innervate both the LC and the spinal cord. These results suggest that the LC may function in parallel to peripheral autonomic systems providing a cognitive complement to sympathetic function, and that the PGi may integrate a wide range of inputs to facilitate adaptive responses to urgent environmental events.