EVIDENCE FOR WIDESPREAD AFFERENTS TO BARRINGTONS NUCLEUS, A BRAIN-STEM REGION RICH IN CORTICOTROPIN-RELEASING HORMONE NEURONS

Supraspinal afferents to the pontine micturition center, Barrington's nucleus, were investigated in the rat by visualization of the retrogra de tracer, cholera-toxin subunit B, in neurons following iontophoretic injection into Barrington's nucleus. Tissue sections from five rats w ith injections primarily localized in Barrington's nucleus revealed nu merous retrogradely labeled neurons throughout all rostrocaudal levels of the periaqueductal gray (particularly its ventrolateral division), in the lateral hypothalamic area (particularly medial to the fornix), and in the medial preoptic nucleus. Retrogradely labeled neurons were also consistently found in the nucleus of the solitary tract, in the vicinity of the lateral reticular nucleus, nucleus paragigantocellular is, parabrachial nucleus, Kolliker-Fuse nucleus, cuneiform nucleus, ra phe nucleus and zona incerta. In the hypothalamus, in addition to the perifornical region, retrogradely labeled neurons were found in all ca ses in the tuberomammillary nucleus, premammillary nucleus, dorsal hyp othalamic area, ventromedial hypothalamic nucleus, and the paraventric ular nucleus. At more rostral levels, in addition to the medial preopt ic area, retrogradely labeled neurons were seen in the bed nucleus of the stria terminalis and in a region just lateral to the supraoptic nu cleus near the medial amygdaloid nucleus. Retrogradely labeled neurons were also observed in the motor, insular, and infralimbic cortices. I njections of anterograde tracers (cholera-toxin subunit B or Phaseolus vulgaris leucoagglutinin) into the Kolliker-Fuse nucleus, the ventrol ateral periaqueductal gray, lateral hypothalamic area, or medial preop tic area, resulted in fiber labeling within Barrington's nucleus, conf irming the retrograde tracing studies. As previously reported, numerou s neurons in Barrington's nucleus were immunoreactive for corticotropi n-releasing hormone. Double-labeling studies revealed afferent fibers from the periaqueductal gray and lateral hypothalamic area overlapping the corticotropin-releasing hormone-immunoreactive neurons of Barring ton's nucleus, and in some cases anterogradely labeled fibers with var cosities appeared to target these neurons. The present results suggest that Barrington's nucleus in the rat receives neuronal inputs from br ainstem nuclei as well as from forebrain limbic structures including h ypothalamic nuclei, the medial preoptic nucleus, and cortical areas in volved in fluid balance or blood pressure regulation. In light of the role of Barrington's nucleus in micturition, the integration of these various inputs may be important for co-ordinating urinary function wit h fluid and cardiovascular homeostasis. Additionally, as neurons in Ba rrington's nucleus are immunoreactive for the stress-related neurohorm one, corticotropin-releasing hormone, these diverse inputs may regulat e stress-related functions of this nucleus.