title: Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor.
abstract: Hypothalamic-pituitary-adrenal axis activation is a hallmark of the stress response. In the case of physical stressors, there is considerable evidence that medullary catecholamine neurones are critical to the activation of the paraventricular nucleus corticotropin-releasing factor cells that constitute the apex of the hypothalamic-pituitary-adrenal axis. In contrast, it has been thought that hypothalamic-pituitary-adrenal axis responses to emotional stressors do not involve brainstem neurones. To investigate this issue we have mapped patterns of restraint-induced neuronal c-fos expression in intact animals and in animals prepared with either paraventricular nucleus-directed injections of a retrograde tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint-induced patterns of neuronal activation within the medulla of intact animals were very similar to those previously reported in response to physical stressors, including the fact that most stressor-responsive, paraventricular nucleus-projecting cells were certainly catecholaminergic and probably noradrenergic. Despite this, the destruction of paraventricular nucleus catecholamine terminals with 6-hydroxydopamine did not alter corticotropin-releasing factor cell responses to restraint. However, animals with ibotenic acid lesions encompassing either the A1 or A2 noradrenergic cell groups displayed significantly suppressed corticotropin-releasing factor cell responses to restraint. Notably, these medullary lesions also suppressed neuronal responses in the medial amygdala, an area that is now considered critical to hypothalamic-pituitary-adrenal axis responses to emotional stressors and that is also known to display a significant increase in noradrenaline turnover during restraint. We conclude that medullary neurones influence corticotropin-releasing factor cell responses to emotional stressors via a multisynaptic pathway that may involve a noradrenergic input to the medial amygdala. These results overturn the idea that hypothalamic-pituitary-adrenal axis response to emotional stressors can occur independently of the brainstem.
authors.affiliation: Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, 4072, Brisbane, Qld, Australia. c.dayas@mailbox.uq.edu.au
authors.forename: C V
authors.initials: CV
authors.lastname: Dayas
authors.forename: K M
authors.initials: KM
authors.lastname: Buller
authors.forename: T A
authors.initials: TA
authors.lastname: Day
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000679:Amygdala / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002452:Cell Count; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003714:Denervation; D017979:Gold Colloid / Q000493:pharmacokinetics; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D009410:Nerve Degeneration / Q000139:chemically induced; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000009:adverse effects; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D014909:Wheat Germ Agglutinins / Q000493:pharmacokinetics
chemical_list: D002395:Catecholamines; D017979:Gold Colloid; D016760:Proto-Oncogene Proteins c-fos; D014909:Wheat Germ Agglutinins; C051777:wheat germ agglutinin-gold; D016627:Oxidopamine; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone