Miles Orchinik
Neurobiology of Stress and Mechanisms of Stress Hormone Action
We are working towards an integrated understanding of how stress alters brain function, with particular emphasis on behavioral and neuroendocrine processes. In all vertebrates, exposure to an array of adverse conditions stimulates a common neuroendocrine response - the release of corticosteroid hormones. A major target for corticosteroids is the brain, where these hormones produce context-specific changes in neuronal function leading to changes in behavior and/or physiology that are critical for dealing with immediate threats. Paradoxically, when this adaptive neuroendocrine response is persistently activated, deleterious alterations in brain function may result. We have studied cellular, molecular and neural mechanisms mediating corticosteroid action in a variety of species. Current projects in the lab include: 1) Investigations of corticosteroid action the dorsomedial hypothalamus, a key site for integrating blood-borne and neural factors during an acute stress response. Corticosteroids appear to regulate serotonin clearance, and therefore neurotransmission, via novel transporters in this brain region. 2) Investigations into the regulation and functional significance of adult neurogenesis in vertebrate brains. Stress is a potent modulator of adult brain cell proliferation, differentiation and survival. We are using an amphibian model to study these processes, with particular interest in the role adult neurogenesis plays in seasonal neuroendocrine regulation.
Selected Publications
Breuner, C.W. and Orchinik, M. (2009) Pharmacological characterization of intracellular, membrane, and plasma binding sites for corticosterone in house sparrows. General and Comparative Endocrinology (epub ahead of print) doi:10.1016/j.ygcen.2009.01.027
Feng, N., Telefont, M., Kelly, K., Orchinik, M., Forster, G.L., Renner, K.L., and Lowry, C.A. (2009) Local perfusion of corticosterone in the rat medial hypothalamus potentiates D-fenfluramine-induced elevations of extracellular 5-HT concentrations: potential role of corticosterone-sensitive organic cation transporter 3 (OCT3). Hormones and Behavior (epub ahead of print) http://dx.doi.org/10.1016/j.yhbeh.2009.03.023
Fokidis, B.K. Orchinik, M., and Deviche, P. (2009) Corticosterone and corticosteroid binding globulin in birds: Relation to urbanization in a desert city. General and Comparative Endocrinology 160(3): 259-270. http://dx.doi.org/10.1016/j.ygcen.2008.12.005
Gasser, P., Orchinik, M., and Lowry, C.A. (2009) Distribution of organic cation transporter 3, a corticosterone-sensitive monoamine transporter, in the rat brain.Journal of Comparative Neurology 512(4): 529-555.
Gasser, P.J., Lowry, C.A., and Orchinik, M. (in press) Rapid Corticosteroid Actions on Behavior: Mechanismsand Implications. In: D.W. Pfaff et al. (Eds.), Hormones, Brain and Behavior, 2nd Ed., Academic Press.
Gasser, P., Lowry, C.A. and Orchinik, M. (2006) Corticosterone-sensitive monoamine transport in the rat dorsomedial hypothalamus: potential role for organic cation transporter 3 in stress-induced modulation of monoaminergic neurotransmission. J.Neurosci. 26(34): 8758-8766.
Feng,N., Mo,B., Johnson,J.L., Orchinik,M., Lowry,C.A., Renner,K.J. (2005) Local inhibition of organic cation transporters increases extracellular serotonin in the medial hypothalamus. Brain Research 1063: 69-76.
Steiner, A.A., Dogan, D., Ivanov, A.I., Patel, S., Rudaya, A.Y., Jennings, D.H., Orchinik, M., Pace, T.W.W., O'Connor, K.A., Watkins, L.R., and Romanovsky, A.A. (2004) A new function of the leptin receptor: mediation of the recovery from lipopolysaccharide hypothermia. FASEB.J. 18(15):1949-61.
Breuner, C.W., Orchinik, M., Hahn, T.P., Meddle, S.L., Moore, I.T., Owen-Ashley, N.T., Sperry, T.S., and Wingfield, J.C. (2003) Differential mechanisms for plasticity of the stress response across latitudinal gradients. American Journal of Physiology: Regulatory, Integrative, and Comparative Physiology 285(3): R594-600.
Breuner, C.W. and Orchinik, M. (2002) Plasma binding proteins as mediators of corticosteroid action in vertebrates. J. Endocrinol. 175: 99-112.
Orchinik, M., Gasser, P., and Breuner, C. Rapid Corticosteroid Actions on Behavior: Cellular Mechanisms and Organismal Consequences. In: D.W. Pfaff et al. (Eds), Hormones, Brain and Behavior, Vol 3: 567-600. Academic Press. New York. 2002.
Orchinik, M., Carroll, S.S., Li, Y.-H., McEwen, B.S. and Weiland, N.G. (2001) Heterogeneity of hippocampal GABAA receptors: regulation by corticosterone. J.Neurosci. 21: 330-339.
Lowry, C.A., Kedzie, K.A., Renner, K.J., Moore, F.L. and Orchinik, M. (2001) Rapid changes in monoamine levels following administration of corticotropin-releasing factor or corticosterone are localized in dorsomedial hypothalamus. Horm.Behav. 39: 195-205.
Deviche, P., Breuner, C. and Orchinik, M. (2001) Testosterone, corticosterone, and photoperiod interact to regulate plasma levels of binding globulin and of free steroid hormone in Dark-eyed Juncos. Gen.Comp.Endocrinol. 122: 67-77.
Breuner, C.W. and Orchinik, M. (2001) Seasonal regulation of membrane and intracellular corticosteroid receptors in the House Sparrow brain. J.Neuroendocrinol. 13: 412-420.
Jennings, D.H., Moore, M.C., Knapp, R., Matthews, L. and Orchinik, M. (2000) Plasma steroid-binding globulin mediation of differences in stress reactivity in alternative male phenotypes in tree lizards, Urosaurus ornatus. Gen.Comp.Endocrinol. 120: 189-199.
Orchinik, M., Matthews, L. and Gasser, P. (2000) Distinct intracellular, membrane-bound, and plasma binding sites for glucocorticoids in an amphibian. Gen.Comp.Endocrinol. 118: 284-301.
Orchinik, M. (1998) Glucocorticoids, stress and behavior: Shifting the timeframe. Hormones and Behavior 34: 320-327.
Orchinik, M., Weiland, N.G., and McEwen, B.S. (1995) Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus. Brain Res.Mol.Brain Res. 34: 29-37.
Rose, J.D., Moore, F.L., and Orchinik, M. (1993) Rapid neurophysiological effects of corticosterone on medullary neurons: relationship to stress-induced suppression of courtship clasping in an amphibian. Neuroendocrinology 57:815-824.
Orchinik, M., Murray, T.F. and Moore, F.L. (1991). A corticosteroid receptor in neuronal membranes. Science 252:1848-1851.