title: Optogenetic elevation of endogenous glucocorticoid level in larval zebrafish.
abstract: The stress response is a suite of physiological and behavioral processes that help to maintain or reestablish homeostasis. Central to the stress response is the hypothalamic-pituitary-adrenal (HPA) axis, as it releases crucial hormones in response to stress. Glucocorticoids (GCs) are the final effector hormones of the HPA axis, and exert a variety of actions under both basal and stress conditions. Despite their far-reaching importance for health, specific GC effects have been difficult to pin-down due to a lack of methods for selectively manipulating endogenous GC levels. Hence, in order to study stress-induced GC effects, we developed a novel optogenetic approach to selectively manipulate the rise of GCs triggered by stress. Using this approach, we could induce both transient hypercortisolic states and persistent forms of hypercortisolaemia in freely behaving larval zebrafish. Our results also established that transient hypercortisolism leads to enhanced locomotion shortly after stressor exposure. Altogether, we present a highly specific method for manipulating the gain of the stress axis with high temporal accuracy, altering endocrine and behavioral responses to stress as well as basal GC levels. Our study offers a powerful tool for the analysis of rapid (non-genomic) and delayed (genomic) GC effects on brain function and behavior, feedbacks within the stress axis and developmental programming by GCs.
authors: Developmental Genetics of the Nervous System, Max Planck Institute for Medical Research Heidelberg, Germany.
authors: Rodrigo J
authors: RJ
authors: De Marco
authors: Antonia H
authors: AH
authors: Groneberg
authors: Chen-Min
authors: CM
authors: Yeh
authors: Luis A
authors: LA
authors: Castillo Ramírez
authors: Soojin
authors: S
authors: Ryu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D005938:Glucocorticoids / Q000378:metabolism*; D007814:Larva; D062308:Optogenetics / Q000379:methods*; D010775:Photic Stimulation / Q000379:methods*; D011235:Predatory Behavior / Q000502:physiology*; D013315:Stress, Psychological / Q000378:metabolism / Q000523:psychology; D013550:Swimming / Q000502:physiology*; D015027:Zebrafish
chemical_list: D005938:Glucocorticoids
keywords: HPA axis; glucocorticoids; larval zebrafish; optogenetics; stress response
references: Ann N Y Acad Sci. 2009 Oct;1179:19-40
references: 19906230
references: Eur J Pharmacol. 2008 Apr 7;583(2-3):174-85
references: 18282566
references: Behav Brain Res. 2009 Dec 14;205(1):38-44
references: 19540270
references: J Physiol. 2006 Apr 1;572(Pt 1):31-44
references: 16469780
references: Mol Cell Endocrinol. 2011 Jan 1;331(1):11-22
references: 20833224
references: Ann N Y Acad Sci. 2009 Oct;1179:56-69
references: 19906232
references: Prog Brain Res. 2008;167:17-34
references: 18037004
references: Ann N Y Acad Sci. 1998 Jun 30;851:311-35
references: 9668623
references: Endocr Rev. 2000 Feb;21(1):55-89
references: 10696570
references: J Neurosci. 2012 Jan 11;32(2):616-25
references: 22238097
references: Curr Biol. 2007 May 15;17(10):873-80
references: 17481897
references: Nat Methods. 2007 Jan;4(1):39-42
references: 17128267
references: Mol Psychiatry. 2013 Jun;18(6):681-91
references: 22641177
references: Biochem Biophys Res Commun. 2005 Oct 7;335(4):1002-7
references: 16111661
references: J Endocrinol. 1976 Jun;69(3):34P-35P
references: 1084910
references: J Comp Neurol. 2007 Nov 20;505(3):235-48
references: 17879270
references: Endocrinology. 1984 Dec;115(6):2368-74
references: 6094157
references: Endocr Rev. 1998 Jun;19(3):269-301
references: 9626555
references: Ann N Y Acad Sci. 1994 Nov 30;746:22-31; discussion 31-2, 64-7
references: 7825879
references: Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):139-62
references: 16303171
references: Neurotoxicology. 2009 Jan;30(1):52-8
references: 18952124
references: Science. 1984 Dec 14;226(4680):1342-4
references: 6334362
references: Ann N Y Acad Sci. 1969 Apr 21;156(2):696-721
references: 4309115
references: Front Neuroendocrinol. 2005 Oct-Dec;26(3-4):103-8
references: 16242180
references: J Endocrinol. 2011 May;209(2):153-67
references: 21357682
references: PLoS Biol. 2007 Apr;5(4):e78
references: 17373855
references: Mol Neurobiol. 1998 Aug;18(1):1-22
references: 9824846
references: Nat Rev Neurosci. 2005 Jun;6(6):463-75
references: 15891777
references: Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R711-9
references: 18077507
references: J Biol Chem. 2010 Dec 31;285(53):41501-8
references: 21030591
references: Curr Opin Neurobiol. 2013 Feb;23(1):119-26
references: 23246238
references: J Neurobiol. 2004 Apr;59(1):147-61
references: 15007833
references: Trends Pharmacol Sci. 2006 Oct;27(10):531-8
references: 16935354
references: ACS Chem Biol. 2012 Jul 20;7(7):1178-83
references: 22545806
references: Aquaculture. 2009 Dec 1;297(1-4):157-162
references: 25587201
references: Nat Clin Pract Endocrinol Metab. 2007 Jun;3(6):479-88
references: 17515892
references: Prog Brain Res. 2008;170:379-88
references: 18655897
references: Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 1;35(6):1432-51
references: 20971150
references: Annu Rev Physiol. 2005;67:259-84
references: 15709959
references: Mol Cell Endocrinol. 2010 May 14;320(1-2):145-52
references: 20138960
references: Nat Protoc. 2010 Nov;5(11):1786-99
references: 21030954
references: N Engl J Med. 1984 Oct 25;311(17):1127
references: 6090905
references: J Exp Biol. 2007 Jul;210(Pt 14):2526-39
references: 17601957
references: Endocrinology. 2010 Oct;151(10):4811-9
references: 20702575
references: Dev Neurobiol. 2012 Mar;72(3):373-85
references: 21567979
references: Zebrafish. 2010 Dec;7(4):349-58
references: 21091199
references: Nat Neurosci. 2004 Aug;7(8):847-54
references: 15220929
references: J Neurosci. 2006 Jun 14;26(24):6643-50
references: 16775153
references: Gen Comp Endocrinol. 2006 Mar;146(1):36-44
references: 16403502
references: Eur J Neurosci. 2006 Sep;24(5):1477-87
references: 16965544
references: J Biol Chem. 2011 Jan 14;286(2):1181-8
references: 21030594
references: J Neurosci. 2009 Jul 8;29(27):8621-9
references: 19587267
references: Am J Physiol. 1978 Jan;234(1):R39-45
references: 203197
references: Mol Endocrinol. 2003 May;17(5):959-66
references: 12576489
references: Brain Res. 1995 Mar 27;675(1-2):297-302
references: 7796142
references: Rev Neurosci. 2011;22(1):49-62
references: 21615261
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14449-54
references: 20663957
references: Gen Comp Endocrinol. 2009 Oct;164(1):61-9
references: 19366623
references: Physiol Rev. 1997 Jul;77(3):591-625
references: 9234959
references: Front Behav Neurosci. 2012 Oct 11;6:68
references: 23087630
references: J Endocrinol. 1972 Dec;55(3):489-97
references: 4345959
references: Behav Brain Res. 2008 Mar 17;188(1):168-77
references: 18054804