Distinct mechanisms underlie activation of hypothalamic neurosecretory neurons and their medullary catecholaminergic afferents in categorically different stress paradigms.

Abstract

Intermittent electrical footshock induces cfos expression in parvocellular neurosecretory neurons expressing corticotropin-releasing factor and in other visceromotor cell types of the paraventricular hypothalamic nucleus (PVH). Since catecholaminergic neurons of the nucleus of the solitary tract and ventrolateral medulla make up the dominant loci of footshock-responsive cells that project to the PVH, these were evaluated as candidate afferent mediators of hypothalamic neuroendocrine responses. Rats bearing discrete unilateral transections of this projection system were exposed to a single 30-min footshock session and sacrificed 2 hr later. Despite depletion of the aminergic innervation on the ipsilateral side, shock-induced up-regulation of Fos protein and corticotropin-releasing factor mRNA were comparable in strength and distribution in the PVH on both sides of the brain. This lesion did, however, result in a substantial reduction of Fos expression in medullary aminergic neurons on the ipsilateral side. These results contrast diametrically with those obtained in a systemic cytokine (interleukin 1) challenge paradigm, where similar cuts ablated the Fos response in the ipsilateral PVH but left intact the induction seen in the ipsilateral medulla. We conclude that (i) footshock-induced activation of medullary aminergic neurons is a secondary consequence of stress, mediated via a descending projection transected by our ablation, (ii) stress-induced activation of medullary aminergic neurons is not necessarily predictive of an involvement of these cell groups in driving hypothalamic visceromotor responses to a given stressor, and (iii) despite striking similarities in the complement of hypothalamic effector neurons and their afferents that may be activated by stresses of different types, distinct mechanisms may underlie adaptive hypothalamic responses in each.Catecholamine-synthesizing neurons of the medulla oblongata provide a massive and functionally important innervation of multiple visceromotor cell types resident within the paraventricular nucleus of the hypothalamus (PVH) (1). This projection arises from adrenergic and noradrenergic neurons in the nucleus of the solitary tract (NTS) and the ventrolateral medullary reticular formation (1-3) and has been implicated in conveying sensory information from the thoracic and abdominal viscera to effect reflex adjustments in the output of parvocellular neurosecretory neurons that express corticotropin-releasing factor (CRF) for the initiation of pituitaryadrenal responses to stress, magnocellular neurosecretory neurons, and cells that project intracerebrally to modulate sensory and motor traffic in central autonomic pathways (4, 5). Although catecholaminergic projections make up the major known ascending input to these effector neuron populations ofThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.the PVH...

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“…Although the specificity for foot shock is an unexpected dimension of the cross-sensitization induced by nicotine SA, it is consistent with an emerging viewpoint on the HPA axis that emphasizes its discriminative rather than ubiquitous responsiveness to diverse stressors (Deak et al, 2005;Li et al, 1996). Such specificity might depend on neuronal plasticity induced by nicotine within brain areas that are preferentially involved in mediating the stress response to psychological stressors.…”

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