Radley JJ, Sawchenko PE (2007) Noradrenergic denervation of dorsal medial prefrontal cortex (mPFC) modulates paraventricular hypothalamic responses to acute restraint stress. Neuroscience 2007 Abstracts 198.4/ZZ13. Society for Neuroscience, San Diego, CA.
Summary: The dorsal mPFC is implicated in restricting the hypothalamo-pituitary-adrenal (HPA) axis response to acute emotional stress via its influence on neuroendocrine effector mechanisms represented in the paraventricular hypothalamic nucleus (PVH). The afferents that provide for mPFC engagement during stress may include ascending noradrenergic projections from the locus coeruleus (LC), which are known to be stress-responsive and capable of modulating attentional mechanisms and other aspects of mPFC function. Arguing against such a role for LC-mPFC projections is evidence that LC lesions attenuate PVH/HPA responses to acute emotional stress. Here we sought to clarify the role of the noradrenergic innervation of mPFC in acute stress-induced PVH activation. Rats received injections of the axonally transported catecholamine immunotoxin, anti-dopamine-β-hydroxylase (DBH)-saporin, centered in the prelimbic area, or sham injections of IgG-saporin or saline. 14 days later, rats were subjected to 30 min of restraint and perfused 2 h later. Immunohistochemical localization of the immediate-early gene product, Fos, was employed as an index of cellular activation in PVH. Cell counts revealed that acute stress reliably provoked marked increases in the number of Fos-labeled neurons in the PVH of all restrained groups relative to unstressed controls. Among stressed groups, anti-DBH-saporin lesions in the dorsal mPFC decreased activational responses in the PVH by 30%, relative to sham-lesioned animals, that were focused in the hypophysiotropic (dorsal medial parvocellular) subdivision. DBH immunostaining revealed a virtually complete noradrenergic denervation of the prelimbic area in immunotoxin-treated animals, while the ventral mPFC (infralimbic area) remained intact. Cortical fields dorsally and laterally adjoining the target area displayed a partial denervation, consistent with local collateralization of prelimbic-projecting LC neurons. While these data are consistent with a role for LC-mPFC projections in facilitating restraint-induced PVH engagement, it remains to be determined how this perspective may be reconciled with prior evidence indicating that mPFC serves normally to inhibit PVH/HPA responses to acute emotional stress.
Related Products: Anti-DBH-SAP (Cat. #IT-03)