ACTIVATION OF NEURONS PROJECTING TO THE PARAVENTRICULAR HYPOTHALAMIC NUCLEUS BY INTRAVENOUS LIPOPOLYSACCHARIDE

The central nervous system interacts with the immune system to coordin ate several components of the acute phase response, although the speci fic neuroanatomical pathways that mediate these responses are still un characterized. However, neurons in both the autonomic and endocrine co mponents of the paraventricular hypothalamic nucleus (PVH) are charact eristically activated in different models of immune stimulation. In th e current study, we have used intravenous administration of lipopolysa ccharide (LPS; 5 or 125 mu g/kg) to induce the acute phase response. W e subsequently coupled immunohistochemistry for Fos (as a marker of ne uronal activation) with retrograde transport of the neuroanatomical tr acer cholera toxin-b from the PVH. Several of the activated cell group s directly projected to the paraventricular nucleus, including the vis ceromotor (infralimbic) cortex, median preoptic nucleus, ventromedial preoptic area, bed nucleus of the stria terminalis, parabrachial nucle us, ventrolateral medulla, and nucleus of the solitary tract. These fi ndings indicate that immune system stimulation activates cell groups f rom multiple nervous system levels that project to the paraventricular nucleus. We hypothesize that the activation of specific autonomic and endocrine elements of the PVH may be due to the activity of distinct afferents that converge on the PVH from multiple components of the cen tral autonomic control system. Our results are consistent with the hyp othesis that the PVH plays a key role in integrating diverse physiolog ical cues into the varied manifestations that constitute the cerebral component of the acute phase response. (C) 199s Wiley-Liss, Inc.