PREPROCHOLECYSTOKININ MESSENGER-RNA-EXPRESSING NEURONS IN THE RAT PARABRACHIAL NUCLEUS - SUBNUCLEAR LOCALIZATION, EFFERENT PROJECTION, AND EXPRESSION OF NOCICEPTIVE-RELATED INTRACELLULAR SIGNALING SUBSTANCES

The pontine parabrachial nucleus (PB) is a major target for ascending fibers from nociresponsive dorsal horn neurons. Several different neur opeptides have been identified in the PB. By using double-labeling met hods that combine in situ hybridization histochemistry with retrograde tract tracing and immunohistochemistry, we have examined the subnucle ar localization of preprocholecystokinin mRNA (ppCCK)-containing neuro ns, investigated their efferent projection, and analyzed their express ion of intracellular signaling substances that may be of importance fo r nociceptive processing. The results show that neurons containing ppC CK are preferentially localized to the superior lateral subnucleus (PB sl), whereas other subnuclei, such, as the dorsal lateral, external la teral, central lateral, and ventral lateral subnuclei, and the Kollike r-Fuse nucleus, contain only moderate to small numbers of such neurons . Injections of the retrograde tracer cholera toxin subunit b into the ventromedial hypothalamus demonstrated that ppCCK-containing neurons in PBsl were projection neurons. Following nociceptive stimulation, th e ppCCK-containing neurons expressed FOS protein as well as phosphoryl ated cyclic AMP-responsive element-binding protein (CREB). In addition , Ca2+/calmodulin-dependent kinase II (CaMKII) was heavily and rather selectively expressed in PBsl and was co-localized to ppCCK-containing neurons. These observations show that nociceptive stimuli activate a cholecystokinin pathway from the parabrachial nucleus to the ventromed ial hypothalamus that may be important for homeostatic responses to ti ssue damage, and point to a putative intracellular route for Ca2+-medi ated FOS transcription via CaMKII and CREB for the regulation of ppCCK transcription. (C) 1998 Wiley-Liss, Inc.