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      Fine Topography of Brain Areas Activated by Cold Stress

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          Neuronal activity in response to acute cold exposure was mapped in the central nervous system of adult rats using Fos immunostaining. A single, 3-hour exposure to cold elicited strong Fos-like immunoreactivity in the medial preoptic nucleus that is known as the thermoregulatory center of the brain. By this technique, pontine and medullary thermosensitive areas have been first localized and outlined anatomically. The medullary thermosensitive neurons occupy well-demarcated areas immediately ventral and dorsal to the spinal trigeminal nucleus, termed peritrigeminal and paratrigeminal nuclei, respectively. Cold-sensitive neurons were present in the dorsal part of the pontine reticular formation. Topographically, this area corresponds to the ‘pontine thermoregulatory area’, named on the basis of neurophysiological observations. In addition, thermosensitive neurons were found in the rostral thalamus and zona incerta. Several cell groups that showed strong Fos-like immunoreactivity in our previous pain-related stress experiments were also activated by cold exposure. The midline thalamic, hypothalamic dorsomedial, supramamillary and lateral parabrachial nuclei were targets of cold stress-induced noxious stimuli. Fos-positive neurons established specific topographical patterns in the paraventricular, arcuate, central amygdaloid nuclei, and the nucleus of the solitary tract. The possible involvement of central noradrenergic neurons in stress response to acute cold exposure was investigated by double immunostaining for tyrosine hydroxylase (TH) and Fos. None of the tyrosine hydroxylase positive neurons in the brain stem established Fos-like immunoreactivity, suggesting that the central noradrenergic system may have a minor, if any, role in cold-induced stress responses. Based on the topographical distribution of Fos-activated neurons, this study suggests that in addition to the hypothalamo-pituitary-adrenal axis, some other stress effector systems may play an important role in the maintenance of homeostasis during cold stress.

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          Most cited references 12

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          Induction of c-fos-like protein in spinal cord neurons following sensory stimulation.

           S Hunt,  Luigi Pini,  G Evan (2015)
          It has been suggested that the proto-oncogenes c-fos and c-myc participate in the control of genetic events which lead to the establishment of prolonged functional changes in neurons. Expression of c-fos and c-myc are among the earliest genetic events induced in cultured fibroblast and phaeochromocytoma cell lines by various stimuli including growth factors, peptides and the intracellular second messengers diacylglycerol, cAMP and Ca2+. We report here that physiological stimulation of rat primary sensory neurons causes the expression of c-fos-protein-like immunoreactivity in nuclei of postsynaptic neurons of the dorsal horn of the spinal cord. Activation of small-diameter cutaneous sensory afferents by noxious heat or chemical stimuli results in the rapid appearance of c-fos-protein-like immunoreactivity in the superficial layers of the dorsal horn. However, activation of low-threshold cutaneous afferents results in fewer labelled cells with a different laminar distribution. No c-fos induction was seen in the dorsal root ganglia, gracile nucleus or ventral horn. Thus, synaptic transmission may induce rapid changes in gene expression in certain postsynaptic neurons.
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            Stress-induced norepinephrine release in the hypothalamic paraventricular nucleus and pituitary-adrenocortical and sympathoadrenal activity: in vivo microdialysis studies.

            The hypothalamic-pituitary-adrenocortical (HPA) axis and the autonomic nervous system are major effector systems that serve to maintain homeostasis during exposure to stressors. In the past decade, interest in neurochemical regulation and in pathways controlling activation of the HPA axis has focused on catecholamines, which are present in high concentrations in specific brain areas--especially in the hypothalamus. The work described in this review has concentrated on the application of in vivo microdialysis in rat brain regions such as the paraventricular nucleus (PVN) of the hypothalamus, the central nucleus of the amygdala (ACE), the bed nucleus of the stria terminalis (BNST), and the posterolateral hypothalamus in order to examine aspects of catecholaminergic function and relationships between altered catecholaminergic function and the HPA axis and sympathoadrenal system activation in stress. Exposure of animals to immobilization (IMMO) markedly and rapidly increases rates of synthesis, release, and metabolism of norepinephrine (NE) in all the brain areas mentioned above and supports previous suggestions that in the PVN NE stimulates release of corticotropin-releasing hormone (CRH). The role of NE in the ACE and the BNST and most other areas possessing noradrenergic innervation remains unclear. Studies involving lower brainstem hemisections show that noradrenergic terminals in the PVN are derived mainly from medullary catecholaminergic groups rather than from the locus ceruleus, which is the main source of NE in the brain. Moreover, the medullary catecholaminergic groups contribute substantially to IMMO-induced noradrenergic activation in the PVN. Data obtained from adrenalectomized rats, with or without glucocorticoid replacement, and from hypercortisolemic rats suggest that glucocorticoids feedback to inhibit CRH release in the PVN, via attenuation of noradrenergic activation. Results from rats exposed to different stressors have indicated substantial differences among stressors in eliciting PVN noradrenergic responses as well as of responses of the HPA, sympathoneural, and adrenomedullary systems. Finally, involvement of other areas that participate in the regulation of the HPA axis such as the ACE, the BNST, and the hippocampus and the importance of stress-induced changes in expression of immediate early genes such as c-fos are discussed.
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              Neurons in the superficial dorsal horn of the rat spinal cord projecting to the medullary ventrolateral reticular formation express c-fos after noxious stimulation of the skin.

              The nociceptive nature of the neurons of the superficial dorsal horn (laminae I-III) which project to the medullary ventrolateral reticular formation is studied in the rat. Medullary injections of Fluoro-Gold showed exclusive retrograde labeling of laminae I-III cells when the tracer filled a zone intermediate between the lateral tip of the lateral reticular nucleus and the spinal trigeminal nucleus, pars caudalis. This zone is here called VLMlat. Following noxious mechanical or thermal stimulation of the skin, double-labeled neurons, which stained retrogradely and were Fos-immunoreactive, prevailed in laminae I and IIo. Double-labeled neurons were few in lamina IIi after thermal stimulation and entirely lacking in lamina III after the two kinds of stimulation. Findings in lamina I confirm previous electrophysiological data (see Menétrey et al., J. Neurophysiol., 52 (1984) 595-611) showing that lamina I cells projecting to the ventrolateral reticular medulla convey noxious messages. The occurrence of numerous double-labeled cells in lamina IIo suggests that this lamina is also involved in nociceptive transmission to the VLMlat.

                Author and article information

                S. Karger AG
                August 2000
                07 September 2000
                : 72
                : 2
                : 102-113
                Laboratory of Neuromorphology, Semmelweis University, Budapest, Hungary
                54577 Neuroendocrinology 2000;72:102–113
                © 2000 S. Karger AG, Basel

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                Page count
                Figures: 14, Tables: 1, References: 62, Pages: 12


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