title: Neuropeptide y gates a stress-induced, long-lasting plasticity in the sympathetic nervous system.
abstract: Acute stress evokes the fight-or-flight reflex, which via release of the catecholamine hormones affects the function of every major organ. Although the reflex is transient, it has lasting consequences that produce an exaggerated response when stress is reexperienced. How this change is encoded is not known. We investigated whether the reflex affects the adrenal component of the sympathetic nervous system, a major branch of the stress response. Mice were briefly exposed to the cold-water forced swim test (FST) which evoked an increase in circulating catecholamines. Although this hormonal response was transient, the FST led to a long-lasting increase in the catecholamine secretory capacity measured amperometrically from chromaffin cells and in the expression of tyrosine hydroxylase. A variety of approaches indicate that these changes are regulated postsynaptically by neuropeptide Y (NPY), an adrenal cotransmitter. Using immunohistochemistry, RT-PCR, and NPY(GFP) BAC mice, we find that NPY is synthesized by all chromaffin cells. Stress failed to increase secretory capacity in NPY knock-out mice. Genetic or pharmacological interference with NPY and Y1 (but not Y2 or Y5) receptor signaling attenuated the stress-induced change in tyrosine hydroxylase expression. These results indicate that, under basal conditions, adrenal signaling is tonically inhibited by NPY, but stress overrides this autocrine negative feedback loop. Because acute stress leads to a lasting increase in secretory capacity in vivo but does not alter sympathetic tone, these postsynaptic changes appear to be an adaptive response. We conclude that the sympathetic limb of the stress response exhibits an activity-dependent form of long-lasting plasticity.
authors.affiliation: Department of Biology, Pennsylvania State University, State College, Pennsylvania 16802, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Manqi
authors.initials: M
authors.lastname: Wang
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Whim
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000311:Adrenal Glands / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005731:Ganglionic Stimulants / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D009478:Neuropeptide Y / Q000172:deficiency / Q000378:metabolism*; D010625:Phenylethanolamine N-Methyltransferase / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology*; D013550:Swimming / Q000523:psychology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D005731:Ganglionic Stimulants; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D049452:Green Fluorescent Proteins; D010625:Phenylethanolamine N-Methyltransferase
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