Skip to main content

Neural Regulation of the Stress Response: The Many Faces of Feedback

Cellular and Molecular Neurobiology volume 32, pages 683–694 (2012)Cite this article

Abstract

The mammalian stress response is an integrated physiological and psychological reaction to real or perceived adversity. Glucocorticoids (GCs) are an important component of this response, acting to redistribute energy resources to both optimize survival in the face of challenge and restore homeostasis after the immediate threat has subsided. Release of GCs is mediated by the hypothalamo–pituitary–adrenocortical (HPA) axis, driven by a neural signal originating in the paraventricular nucleus (PVN). Stress levels of GCs bind to glucocorticoid receptors (GRs) in multiple body compartments, including brain, and consequently have wide-reaching actions. For this reason, GCs serve a vital function in feedback inhibition of their own secretion. Fast, non-genomic feedback inhibition of the HPA axis is mediated at least in part by GC signaling in the PVN, acting by a cannabinoid-dependent mechanism to rapidly reduce both neural activity and GC release. Delayed feedback termination of the HPA axis response is mediated by forebrain GRs, presumably by genomic mechanisms. GCs also act in the brainstem to attenuate neuropeptidergic excitatory input to the PVN via acceleration of mRNA degradation, providing a mechanism to attenuate future responses to stressors. Thus, rather than having a single defined feedback switch, GCs work through multiple neurocircuits and signaling mechanisms to coordinate HPA axis activity to suit the overall needs of multiple body systems.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Abbreviations

ACTH:

Adrenocorticotropin

BLA:

Basolateral amygdala

BST:

Bed nucleus of the stria terminalis

CB1:

Type 1 cannabinoid receptor

CeA:

Central nucleus of the amygdala

CRH:

Corticotropin-releasing hormone

DMH:

Dorsomedial hypothalamus

eCB:

Endocannabinoid

GC:

Glucocorticoid

GLP-1:

Glucagon-like peptide-1

GR:

Glucocorticoid receptor

GSE:

Glucocorticoid-induced suppression of excitation

HPA:

Hypothalamo–pituitary–adrenocortical

ilPFC:

Infralimbic prefrontal cortex

MDD:

Major depressive disorder

mGR:

Membrane-associated GR

mPFC:

Medial prefrontal cortex

MR:

Mineralocorticoid receptor

NTS:

Nucleus of the solitary tract

plPFC:

Prelimbic prefrontal cortex

POA:

Preoptic area

PPG:

Preproglucagon

PTSD:

Post-traumatic stress disorder

PVN:

Paraventricular nucleus

References

  • Adam TC, Epel ES (2007) Stress, eating and the reward system. Physiol Behav 91:449–458

    PubMed  CAS  Article  Google Scholar 

  • Bartanusz V, Muller D, Gaillard RC, Streit P, Vutskits L, Kiss JZ (2004) Local gamma-aminobutyric acid and glutamate circuit control of hypophyseotrophic corticotropin-releasing factor neuron activity in the paraventricular nucleus of the hypothalamus. Eur J Neurosci 19:777–782

    PubMed  CAS  Article  Google Scholar 

  • Beaulieu S, Di Paolo T, Barden N (1986) Control of ACTH secretion by the central nucleus of the amygdala: implication of the serotoninergic system and its relevance to the glucocorticoid delayed negative feedback mechanism. Neuroendocrinology 44:247–254

    PubMed  CAS  Article  Google Scholar 

  • Beaulieu S, Di Paolo T, Cote J, Barden N (1987) Participation of the central amygdaloid nucleus in the response of adrenocorticotropin secretion to immobilization stress: opposing roles of the noradrenergic and dopaminergic systems. Neuroendocrinology 45:37–46

    PubMed  CAS  Article  Google Scholar 

  • Belanoff JK, Flores BH, Kalezhan M, Sund B, Schatzberg AF (2001) Rapid reversal of psychotic depression using mifepristone. J Clin Psychopharmacol 21:516–521

    PubMed  CAS  Article  Google Scholar 

  • Bhatnagar S, Huber R, Nowak N, Trotter P (2002) Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint. J Neuroendocrinol 14:403–410

    PubMed  CAS  Article  Google Scholar 

  • Bhatnagar S, Vining C, Denski K (2004) Regulation of chronic stress-induced changes in hypothalamic-pituitary-adrenal activity by the basolateral amygdala. Ann N Y Acad Sci 1032:315–319

    PubMed  CAS  Article  Google Scholar 

  • Boudaba C, Szabo K, Tasker JG (1996) Physiological mapping of local inhibitory inputs to the hypothalamic paraventricular nucleus. J Neurosci 16:7151–7160

    PubMed  CAS  Google Scholar 

  • Boyle MP, Brewer JA, Funatsu M, Wozniak DF, Tsien JZ, Izumi Y, Muglia LJ (2005) Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proc Natl Acad Sci USA 102:473–478

    PubMed  CAS  Article  Google Scholar 

  • Breivogel CS, Childers SR (1998) The functional neuroanatomy of brain cannabinoid receptors. Neurobiol Dis 5:417–431

    PubMed  CAS  Article  Google Scholar 

  • Bronnegard M, Arner P, Hellstrom L, Akner G, Gustafsson JA (1990) Glucocorticoid receptor messenger ribonucleic acid in different regions of human adipose tissue. Endocrinology 127:1689–1696

    PubMed  CAS  Article  Google Scholar 

  • Carroll BJ, Schroeder K, Mukhopadhyay S, Greden JF, Feinberg M, Ritchie J, Tarika J (1980) Plasma dexamethasone concentrations and cortisol suppression response in patients with endogenous depression. J Clin Endocrinol Metab 51:433–437

    PubMed  CAS  Article  Google Scholar 

  • Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP (2007) Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs. J Neurosci 27:2025–2034

    PubMed  CAS  Article  Google Scholar 

  • Choi DC, Evanson NK, Furay AR, Ulrich-Lai YM, Ostrander MM, Herman JP (2008a) The anteroventral bed nucleus of the stria terminalis differentially regulates hypothalamic-pituitary-adrenocortical axis responses to acute and chronic stress. Endocrinology 149:818–826

    PubMed  CAS  Article  Google Scholar 

  • Choi DC, Furay AR, Evanson NK, Ulrich-Lai YM, Nguyen MM, Ostrander MM, Herman JP (2008b) The role of the posterior medial bed nucleus of the stria terminalis in modulating hypothalamic-pituitary-adrenocortical axis responsiveness to acute and chronic stress. Psychoneuroendocrinology 33:659–669

    PubMed  CAS  Article  Google Scholar 

  • Cole RL, Sawchenko PE (2002) Neurotransmitter regulation of cellular activation and neuropeptide gene expression in the paraventricular nucleus of the hypothalamus. J Neurosci 22:959–969

    PubMed  CAS  Google Scholar 

  • Cook CJ (2002) Glucocorticoid feedback increases the sensitivity of the limbic system to stress. Physiol Behav 75:455–464

    PubMed  CAS  Article  Google Scholar 

  • Cota D, Steiner MA, Marsicano G, Cervino C, Herman JP, Grubler Y, Stalla J, Pasquali R, Lutz B, Stalla GK, Pagotto U (2007) Requirement of cannabinoid receptor type 1 for the basal modulation of hypothalamic-pituitary-adrenal axis function. Endocrinology 148:1574–1581

    PubMed  CAS  Article  Google Scholar 

  • Cullinan WE, Herman JP, Watson SJ (1993) Ventral subicular interaction with the hypothalamic paraventricular nucleus: evidence for a relay in the bed nucleus of the stria terminalis. J Comp Neurol 332:1–20

    PubMed  CAS  Article  Google Scholar 

  • Cullinan WE, Herman JP, Battaglia DF, Akil H, Watson SJ (1995) Pattern and time course of immediate early gene expression in rat brain following acute stress. Neuroscience 64:477–505

    PubMed  CAS  Article  Google Scholar 

  • Cunningham ET Jr, Sawchenko PE (1988) Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol 274:60–76

    PubMed  Article  Google Scholar 

  • Cunningham ET Jr, Bohn MC, Sawchenko PE (1990) Organization of adrenergic inputs to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Comp Neurol 292:651–667

    PubMed  Article  Google Scholar 

  • Dallman MF (2005) Fast glucocorticoid actions on brain: back to the future. Front Neuroendocrinol 26:103–108

    PubMed  CAS  Article  Google Scholar 

  • Dallman MF, Jones MT (1973) Corticosteroid feedback control of ACTH secretion: effect of stress-induced corticosterone secretion on subsequent stress responses in the rat. Endocrinology 92:1367–1375

    PubMed  CAS  Article  Google Scholar 

  • Dallman MF, Yates FE (1969) Dynamic asymmetries in the corticosteroid feedback path and distribution-metabolism-binding elements of the adrenocortical system. Ann N Y Acad Sci 156:696–721

    PubMed  CAS  Article  Google Scholar 

  • Dallman MF, Akana SF, Cascio CS, Darlington DN, Jacobson L, Levin N (1987) Regulation of ACTH secretion: variations on a theme of B. Recent Prog Horm Res 43:113–173

    PubMed  CAS  Google Scholar 

  • Dallman MF, Pecoraro N, Akana SF, La Fleur SE, Gomez F, Houshyar H, Bell ME, Bhatnagar S, Laugero KD, Manalo S (2003) Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci USA 100:11696–11701

    PubMed  CAS  Article  Google Scholar 

  • Daniels WM, Richter L, Stein DJ (2004) The effects of repeated intra-amygdala CRF injections on rat behavior and HPA axis function after stress. Metab Brain Dis 19:15–23

    PubMed  CAS  Article  Google Scholar 

  • Dayas CV, Buller KM, Day TA (1999) Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala. Eur J Neurosci 11:2312–2322

    PubMed  CAS  Article  Google Scholar 

  • Dayas CV, Buller KM, Crane JW, Xu Y, Day TA (2001) Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups. Eur J Neurosci 14:1143–1152

    PubMed  CAS  Article  Google Scholar 

  • de Jong IE, de Kloet ER (2004) Glucocorticoids and vulnerability to psychostimulant drugs: toward substrate and mechanism. Ann N Y Acad Sci 1018:192–198

    PubMed  Article  CAS  Google Scholar 

  • de Kloet ER, Reul JM (1987) Feedback action and tonic influence of corticosteroids on brain function: a concept arising from the heterogeneity of brain receptor systems. Psychoneuroendocrinology 12:83–105

    PubMed  Article  Google Scholar 

  • de Kloet ER, Sarabdjitsingh RA (2008) Everything has rhythm: focus on glucocorticoid pulsatility. Endocrinology 149:3241–3243

    PubMed  Article  CAS  Google Scholar 

  • de Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269–301

    PubMed  Article  Google Scholar 

  • de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475

    PubMed  Article  CAS  Google Scholar 

  • Di S, Malcher-Lopes R, Halmos KC, Tasker JG (2003) Nongenomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J Neurosci 23:4850–4857

    PubMed  CAS  Google Scholar 

  • Di S, Malcher-Lopes R, Marcheselli VL, Bazan NG, Tasker JG (2005) Rapid glucocorticoid-mediated endocannabinoid release and opposing regulation of glutamate and gamma-aminobutyric acid inputs to hypothalamic magnocellular neurons. Endocrinology 146:4292–4301

    PubMed  CAS  Article  Google Scholar 

  • Di S, Maxson MM, Franco A, Tasker JG (2009) Glucocorticoids regulate glutamate and GABA synapse-specific retrograde transmission via divergent nongenomic signaling pathways. J Neurosci 29:393–401

    PubMed  CAS  Article  Google Scholar 

  • Diorio D, Viau V, Meaney MJ (1993) The role of the medial prefrontal cortex (cingulate gyrus) in the regulation of hypothalamic-pituitary-adrenal responses to stress. J Neurosci 13:3839–3847

    PubMed  CAS  Google Scholar 

  • Dong HW, Swanson LW (2004a) Organization of axonal projections from the anterolateral area of the bed nuclei of the stria terminalis. J Comp Neurol 468:277–298

    PubMed  Article  Google Scholar 

  • Dong HW, Swanson LW (2004b) Projections from bed nuclei of the stria terminalis, posterior division: implications for cerebral hemisphere regulation of defensive and reproductive behaviors. J Comp Neurol 471:396–433

    PubMed  Article  Google Scholar 

  • Dong HW, Swanson LW (2006) Projections from bed nuclei of the stria terminalis, anteromedial area: cerebral hemisphere integration of neuroendocrine, autonomic, and behavioral aspects of energy balance. J Comp Neurol 494:142–178

    PubMed  Article  Google Scholar 

  • Dong HW, Petrovich GD, Swanson LW (2001a) Topography of projections from amygdala to bed nuclei of the stria terminalis. Brain Res Brain Res Rev 38:192–246

    PubMed  CAS  Article  Google Scholar 

  • Dong HW, Petrovich GD, Watts AG, Swanson LW (2001b) Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain. J Comp Neurol 436:430–455

    PubMed  CAS  Article  Google Scholar 

  • Drevets WC (1999) Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci 877:614–637

    PubMed  CAS  Article  Google Scholar 

  • Dunn JD, Whitener J (1986) Plasma corticosterone responses to electrical stimulation of the amygdaloid complex: cytoarchitectural specificity. Neuroendocrinology 42:211–217

    PubMed  CAS  Article  Google Scholar 

  • Evanson NK, Tasker JG, Hill MN, Hillard CJ, Herman JP (2010) Fast feedback inhibition of the HPA axis by glucocorticoids is mediated by endocannabinoid signaling. Endocrinology 151:4811–4819

    PubMed  CAS  Article  Google Scholar 

  • Feldman S, Weidenfeld J (1998) The excitatory effects of the amygdala on hypothalamo-pituitary-adrenocortical responses are mediated by hypothalamic norepinephrine, serotonin, and CRF-41. Brain Res Bull 45:389–393

    PubMed  CAS  Article  Google Scholar 

  • Feldman S, Conforti N, Itzik A, Weidenfeld J (1994) Differential effect of amygdaloid lesions on CRF-41, ACTH and corticosterone responses following neural stimuli. Brain Res 658:21–26

    PubMed  CAS  Article  Google Scholar 

  • Figueiredo HF, Bruestle A, Bodie B, Dolgas CM, Herman JP (2003) The medial prefrontal cortex differentially regulates stress-induced c-fos expression in the forebrain depending on type of stressor. Eur J Neurosci 18:2357–2364

    PubMed  Article  Google Scholar 

  • Frank MG, Watkins LR, Maier SF (2011) Stress- and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse. Brain Behav Immun 25(Suppl 1):S21–S28

    PubMed  CAS  Article  Google Scholar 

  • Furay AR, Bruestle AE, Herman JP (2008) The role of the forebrain glucocorticoid receptor in acute and chronic stress. Endocrinology 149:5482–5490

    PubMed  CAS  Article  Google Scholar 

  • Fuxe K, Cintra A, Agnati LF, Harfstrand A, Wikstrom AC, Okret S, Zoli M, Miller LS, Greene JL, Gustafsson JA (1987) Studies on the cellular localization and distribution of glucocorticoid receptor and estrogen receptor immunoreactivity in the central nervous system of the rat and their relationship to the monoaminergic and peptidergic neurons of the brain. J Steroid Biochem 27:159–170

    PubMed  CAS  Article  Google Scholar 

  • Ginsberg AB, Pecoraro NC, Warne JP, Horneman HF, Dallman MF (2010) Rapid alteration of stress-induced hypothalamic-pituitary-adrenal hormone secretion in the rat: a comparison of glucocorticoids and cannabinoids. Stress 13:248–257

    PubMed  CAS  Article  Google Scholar 

  • Grillo C, Vallee S, McEwen BS, De Nicola AF (1990) Properties and distribution of binding sites for the mineralocorticoid receptor antagonist [3H]ZK 91587 in brain. J Steroid Biochem 35:11–15

    PubMed  CAS  Article  Google Scholar 

  • Groeneweg FL, Karst H, de Kloet ER, Joels M (2011) Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling. Mol Cell Endocrinol. http://dx.doi.org/10.1016/j.mce.2011.06.020

  • Harfstrand A (1987) Brain neuropeptide Y mechanisms. Basic aspects and involvement in cardiovascular and neuroendocrine regulation. Acta Physiol Scand Suppl 565:1–83

    PubMed  CAS  Google Scholar 

  • Haam J, Halmos KC, Muglia LJ, Tasker JG (2010) Rapid synaptic modulation of hypothalamic neurons by glucocorticoids requires the glucocorticoid receptor. In: Society for Neuroscience. Society for Neuroscience, San Diego, CA, Program No. 389, 19 p

  • Herman JP, Mueller NK (2006) Role of the ventral subiculum in stress integration. Behav Brain Res 174:215–224

    PubMed  CAS  Article  Google Scholar 

  • Herman JP, Schafer MK, Young EA, Thompson R, Douglass J, Akil H, Watson SJ (1989) Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. J Neurosci 9:3072–3082

    PubMed  CAS  Google Scholar 

  • Herman JP, Cullinan WE, Watson SJ (1994) Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression. J Neuroendocrinol 6:433–442

    PubMed  CAS  Article  Google Scholar 

  • Herman JP, Cullinan WE, Ziegler DR, Tasker JG (2002) Role of the paraventricular nucleus microenvironment in stress integration. Eur J Neurosci 16:381–385

    PubMed  Article  Google Scholar 

  • Herman JP, Figueiredo H, Mueller NK, Ulrich-Lai Y, Ostrander MM, Choi DC, Cullinan WE (2003) Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness. Front Neuroendocrinol 24:151–180

    PubMed  CAS  Article  Google Scholar 

  • Hill MN, McEwen BS (2010) Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog Neuropsychopharmacol Biol Psychiatry 34:791–797

    PubMed  CAS  Article  Google Scholar 

  • Hurley KM, Herbert H, Moga MM, Saper CB (1991) Efferent projections of the infralimbic cortex of the rat. J Comp Neurol 308:249–276

    PubMed  CAS  Article  Google Scholar 

  • Jaferi A, Bhatnagar S (2006) Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress. Endocrinology 147:4917–4930

    PubMed  CAS  Article  Google Scholar 

  • Jaferi A, Nowak N, Bhatnagar S (2003) Negative feedback functions in chronically stressed rats: role of the posterior paraventricular thalamus. Physiol Behav 78:365–373

    PubMed  CAS  Article  Google Scholar 

  • Jankord R, Herman JP (2008) Limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress. Ann N Y Acad Sci 1148:64–73

    PubMed  Article  Google Scholar 

  • Johnson LR, Farb C, Morrison JH, McEwen BS, LeDoux JE (2005) Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala. Neuroscience 136:289–299

    PubMed  CAS  Article  Google Scholar 

  • Jones KR, Myers B, Herman JP (2011) Stimulation of the prelimbic cortex differentially modulates neuroendocrine responses to psychogenic and systemic stressors. Physiol Behav 104:266–271

    PubMed  CAS  Article  Google Scholar 

  • Jorgensen H, Knigge U, Kjaer A, Vadsholt T, Warberg J (1998) Serotonergic involvement in stress-induced ACTH release. Brain Res 811:10–20

    PubMed  CAS  Article  Google Scholar 

  • Kanner AM (2009) Depression and epilepsy: do glucocorticoids and glutamate explain their relationship? Curr Neurol Neurosci Rep 9:307–312

    PubMed  CAS  Article  Google Scholar 

  • Kiss A, Palkovits M, Aguilera G (1996) Neural regulation of corticotropin releasing hormone (CRH) and CRH receptor mRNA in the hypothalamic paraventricular nucleus in the rat. J Neuroendocrinol 8:103–112

    PubMed  CAS  Article  Google Scholar 

  • Kolber BJ, Roberts MS, Howell MP, Wozniak DF, Sands MS, Muglia LJ (2008) Central amygdala glucocorticoid receptor action promotes fear-associated CRH activation and conditioning. Proc Natl Acad Sci USA 105:12004–12009

    PubMed  CAS  Article  Google Scholar 

  • Komatsuzaki Y, Murakami G, Tsurugizawa T, Mukai H, Tanabe N, Mitsuhashi K, Kawata M, Kimoto T, Ooishi Y, Kawato S (2005) Rapid spinogenesis of pyramidal neurons induced by activation of glucocorticoid receptors in adult male rat hippocampus. Biochem Biophys Res Commun 335:1002–1007

    PubMed  CAS  Article  Google Scholar 

  • Krettek JE, Price JL (1977) Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat. J Comp Neurol 172:687–722

    PubMed  CAS  Article  Google Scholar 

  • Krishnan V, Nestler EJ (2010) Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 167:1305–1320

    PubMed  Article  Google Scholar 

  • Li HY, Ericsson A, Sawchenko PE (1996) Distinct mechanisms underlie activation of hypothalamic neurosecretory neurons and their medullary catecholaminergic afferents in categorically different stress paradigms. Proc Natl Acad Sci USA 93:2359–2364

    PubMed  CAS  Article  Google Scholar 

  • Lowry CA (2002) Functional subsets of serotonergic neurones: implications for control of the hypothalamic-pituitary-adrenal axis. J Neuroendocrinol 14:911–923

    PubMed  CAS  Article  Google Scholar 

  • Ma S, Morilak DA (2005) Norepinephrine release in medial amygdala facilitates activation of the hypothalamic-pituitary-adrenal axis in response to acute immobilisation stress. J Neuroendocrinol 17:22–28

    PubMed  CAS  Article  Google Scholar 

  • Malcher-Lopes R, Di S, Marcheselli VS, Weng FJ, Stuart CT, Bazan NG, Tasker JG (2006) Opposing crosstalk between leptin and glucocorticoids rapidly modulates synaptic excitation via endocannabinoid release. J Neurosci 26:6643–6650

    PubMed  CAS  Article  Google Scholar 

  • Malcher-Lopes R, Franco A, Tasker JG (2008) Glucocorticoids shift arachidonic acid metabolism toward endocannabinoid synthesis: a non-genomic anti-inflammatory switch. Eur J Pharmacol 583:322–339

    PubMed  CAS  Article  Google Scholar 

  • Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH (2005) Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660

    PubMed  CAS  Article  Google Scholar 

  • McEwen BS, Kalia M (2010) The role of corticosteroids and stress in chronic pain conditions. Metabolism 59(Suppl 1):S9–S15

    PubMed  CAS  Article  Google Scholar 

  • McEwen BS, Weiss JM, Schwartz LS (1968) Selective retention of corticosterone by limbic structures in rat brain. Nature 220:911–912

    PubMed  CAS  Article  Google Scholar 

  • Merchenthaler I, Lane M, Shughrue P (1999) Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol 403:261–280

    PubMed  CAS  Article  Google Scholar 

  • Miller AH, Spencer RL, Pulera M, Kang S, McEwen BS, Stein M (1992) Adrenal steroid receptor activation in rat brain and pituitary following dexamethasone: implications for the dexamethasone suppression test. Biol Psychiatry 32:850–869

    PubMed  CAS  Article  Google Scholar 

  • Mueller NK, Dolgas CM, Herman JP (2004) Stressor-selective role of the ventral subiculum in regulation of neuroendocrine stress responses. Endocrinology 145:3763–3768

    PubMed  CAS  Article  Google Scholar 

  • Mueller NK, Dolgas CM, Herman JP (2006) Regulation of forebrain GABAergic stress circuits following lesion of the ventral subiculum. Brain Res 1116:132–142

    PubMed  CAS  Article  Google Scholar 

  • Myers B, Greenwood-Van Meerveld B (2011) Differential involvement of amygdala corticosteroid receptors in visceral hyperalgesia following acute or repeated stress. Am J Physiol Gastrointest Liver Physiol 302(2):G260–G266

    Google Scholar 

  • Myers B, Dittmeyer K, Greenwood-Van Meerveld B (2007) Involvement of amygdaloid corticosterone in altered visceral and somatic sensation. Behav Brain Res 181:163–167

    PubMed  CAS  Article  Google Scholar 

  • Myers-Schulz B, Koenigs M (2011) Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders. Mol Psychiatry. doi:10.1038/mp.2011.88

  • Ostrander MM, Richtand NM, Herman JP (2003) Stress and amphetamine induce Fos expression in medial prefrontal cortex neurons containing glucocorticoid receptors. Brain Res 990:209–214

    PubMed  CAS  Article  Google Scholar 

  • Pare D, Smith Y, Pare JF (1995) Intra-amygdaloid projections of the basolateral and basomedial nuclei in the cat: phaseolus vulgaris-leucoagglutinin anterograde tracing at the light and electron microscopic level. Neuroscience 69:567–583

    PubMed  CAS  Article  Google Scholar 

  • Patel S, Roelke CT, Rademacher DJ, Cullinan WE, Hillard CJ (2004) Endocannabinoid signaling negatively modulates stress-induced activation of the hypothalamic-pituitary-adrenal axis. Endocrinology 145:5431–5438

    PubMed  CAS  Article  Google Scholar 

  • Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879–886

    PubMed  Article  Google Scholar 

  • Plotsky PM (1987) Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation after activation of catecholaminergic pathways or central norepinephrine injection. Endocrinology 121:924–930

    PubMed  CAS  Article  Google Scholar 

  • Plotsky PM, Cunningham ET Jr, Widmaier EP (1989) Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocr Rev 10:437–458

    PubMed  CAS  Article  Google Scholar 

  • Prager EM, Brielmaier J, Bergstrom HC, McGuire J, Johnson LR (2010) Localization of mineralocorticoid receptors at mammalian synapses. PLoS One 5:e14344

    PubMed  CAS  Article  Google Scholar 

  • Prewitt CM, Herman JP (1998) Anatomical interactions between the central amygdaloid nucleus and the hypothalamic paraventricular nucleus of the rat: a dual tract-tracing analysis. J Chem Neuroanat 15:173–185

    PubMed  CAS  Article  Google Scholar 

  • Radley JJ, Sawchenko PE (2011) A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response. J Neurosci 31:9683–9695

    PubMed  CAS  Article  Google Scholar 

  • Radley JJ, Arias CM, Sawchenko PE (2006) Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. J Neurosci 26:12967–12976

    PubMed  CAS  Article  Google Scholar 

  • Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR (2008) Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J Comp Neurol 507:1141–1150

    PubMed  Article  Google Scholar 

  • Radley JJ, Gosselink KL, Sawchenko PE (2009) A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response. J Neurosci 29:7330–7340

    PubMed  CAS  Article  Google Scholar 

  • Radley JJ, Kabbaj M, Jacobson L, Heydendael W, Yehuda R, Herman JP (2011) Stress risk factors and stress-related pathology: neuroplasticity, epigenetics and endophenotypes. Stress 14:481–497

    PubMed  Google Scholar 

  • Reul JM, de Kloet ER (1985) Two receptor systems for corticosterone in rat brain: microdistribution and differential occupation. Endocrinology 117:2505–2511

    PubMed  CAS  Article  Google Scholar 

  • Rinaman L (2007) Visceral sensory inputs to the endocrine hypothalamus. Front Neuroendocrinol 28:50–60

    PubMed  CAS  Article  Google Scholar 

  • Roland BL, Sawchenko PE (1993) Local origins of some GABAergic projections to the paraventricular and supraoptic nuclei of the hypothalamus in the rat. J Comp Neurol 332:123–143

    PubMed  CAS  Article  Google Scholar 

  • Roozendaal B (2002) Stress and memory: opposing effects of glucocorticoids on memory consolidation and memory retrieval. Neurobiol Learn Mem 78:578–595

    PubMed  CAS  Article  Google Scholar 

  • Roozendaal B, Koolhaas JM, Bohus B (1991) Attenuated cardiovascular, neuroendocrine, and behavioral responses after a single footshock in central amygdaloid lesioned male rats. Physiol Behav 50:771–775

    PubMed  CAS  Article  Google Scholar 

  • Roozendaal B, Koolhaas JM, Bohus B (1992) Central amygdaloid involvement in neuroendocrine correlates of conditioned stress responses. J Neuroendocrinol 4:483–489

    PubMed  CAS  Article  Google Scholar 

  • Sah P, Faber ES, Lopez De Armentia M, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83:803–834

    PubMed  CAS  Google Scholar 

  • Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7:284–301

    PubMed  CAS  Article  Google Scholar 

  • Sawchenko PE, Swanson LW (1983) The organization of forebrain afferents to the paraventricular and supraoptic nuclei of the rat. J Comp Neurol 218:121–144

    PubMed  CAS  Article  Google Scholar 

  • Sawchenko PE, Swanson LW, Steinbusch HW, Verhofstad AA (1983) The distribution and cells of origin of serotonergic inputs to the paraventricular and supraoptic nuclei of the rat. Brain Res 277:355–360

    PubMed  CAS  Article  Google Scholar 

  • Sawchenko PE, Swanson LW, Grzanna R, Howe PR, Bloom SR, Polak JM (1985) Colocalization of neuropeptide Y immunoreactivity in brainstem catecholaminergic neurons that project to the paraventricular nucleus of the hypothalamus. J Comp Neurol 241:138–153

    PubMed  CAS  Article  Google Scholar 

  • Schulkin J, Gold PW, McEwen BS (1998) Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load. Psychoneuroendocrinology 23:219–243

    PubMed  CAS  Article  Google Scholar 

  • Sharma ST, Nieman LK (2011) Cushing’s syndrome: all variants, detection, and treatment. Endocrinol Metab Clin North Am 40:379–391 viii-ix

    PubMed  CAS  Article  Google Scholar 

  • Shepard JD, Barron KW, Myers DA (2000) Corticosterone delivery to the amygdala increases corticotropin-releasing factor mRNA in the central amygdaloid nucleus and anxiety-like behavior. Brain Res 861:288–295

    PubMed  CAS  Article  Google Scholar 

  • Shepard JD, Barron KW, Myers DA (2003) Stereotaxic localization of corticosterone to the amygdala enhances hypothalamo-pituitary-adrenal responses to behavioral stress. Brain Res 963:203–213

    PubMed  CAS  Article  Google Scholar 

  • Shepard JD, Schulkin J, Myers DA (2006) Chronically elevated corticosterone in the amygdala increases corticotropin releasing factor mRNA in the dorsolateral bed nucleus of stria terminalis following duress. Behav Brain Res 174:193–196

    PubMed  CAS  Article  Google Scholar 

  • Singewald GM, Rjabokon A, Singewald N, Ebner K (2011) The modulatory role of the lateral septum on neuroendocrine and behavioral stress responses. Neuropsychopharmacology 36:793–804

    PubMed  Article  Google Scholar 

  • Smith AD, Castro SL, Zigmond MJ (2002) Stress-induced Parkinson’s disease: a working hypothesis. Physiol Behav 77:527–531

    PubMed  CAS  Article  Google Scholar 

  • Solomon MB, Jones K, Packard BA, Herman JP (2010) The medial amygdala modulates body weight but not neuroendocrine responses to chronic stress. J Neuroendocrinol 22:13–23

    PubMed  CAS  Article  Google Scholar 

  • Sotiropoulos I, Cerqueira JJ, Catania C, Takashima A, Sousa N, Almeida OF (2008) Stress and glucocorticoid footprints in the brain-the path from depression to Alzheimer’s disease. Neurosci Biobehav Rev 32:1161–1173

    PubMed  CAS  Article  Google Scholar 

  • Staiger JF, Nurnberger F (1991) The efferent connections of the lateral septal nucleus in the guinea pig: intrinsic connectivity of the septum and projections to other telencephalic areas. Cell Tissue Res 264:415–426

    PubMed  CAS  Article  Google Scholar 

  • Stellato C (2004) Post-transcriptional and nongenomic effects of glucocorticoids. Proc Am Thorac Soc 1:255–263

    PubMed  Article  CAS  Google Scholar 

  • Stevens DR, Gallagher JP, Shinnick-Gallagher P (1987) In vitro studies of the role of gamma-aminobutyric acid in inhibition in the lateral septum of the rat. Synapse 1:184–190

    PubMed  CAS  Article  Google Scholar 

  • Sullivan RM, Gratton A (1998) Relationships between stress-induced increases in medial prefrontal cortical dopamine and plasma corticosterone levels in rats: role of cerebral laterality. Neuroscience 83:81–91

    PubMed  CAS  Article  Google Scholar 

  • Sullivan RM, Gratton A (1999) Lateralized effects of medial prefrontal cortex lesions on neuroendocrine and autonomic stress responses in rats. J Neurosci 19:2834–2840

    PubMed  CAS  Google Scholar 

  • Swanson LW, Petrovich GD (1998) What is the amygdala? Trends Neurosci 21:323–331

    PubMed  CAS  Article  Google Scholar 

  • Swanson LW, Sawchenko PE, Rivier J, Vale WW (1983) Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology 36:165–186

    PubMed  CAS  Article  Google Scholar 

  • Tasker JG, Herman JP (2011) Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic-pituitary-adrenal axis. Stress 14:398–406

    PubMed  CAS  Google Scholar 

  • Tauchi M, Zhang R, D’Alessio DA, Stern JE, Herman JP (2008) Distribution of glucagon-like peptide-1 immunoreactivity in the hypothalamic paraventricular and supraoptic nuclei. J Chem Neuroanat 36:144–149

    PubMed  CAS  Article  Google Scholar 

  • Uhart M, Wand GS (2009) Stress, alcohol and drug interaction: an update of human research. Addict Biol 14:43–64

    PubMed  CAS  Article  Google Scholar 

  • Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci 10:397–409

    PubMed  CAS  Article  Google Scholar 

  • Ulrich-Lai YM, Jones KR, Ziegler DR, Cullinan WE, Herman JP (2011) Forebrain origins of glutamatergic innervation to the rat paraventricular nucleus of the hypothalamus: differential inputs to the anterior versus posterior subregions. J Comp Neurol 519:1301–1319

    PubMed  CAS  Article  Google Scholar 

  • Vale W, Spiess J, Rivier C, Rivier J (1981) Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 213:1394–1397

    PubMed  CAS  Article  Google Scholar 

  • Van de Kar LD, Piechowski RA, Rittenhouse PA, Gray TS (1991) Amygdaloid lesions: differential effect on conditioned stress and immobilization-induced increases in corticosterone and renin secretion. Neuroendocrinology 54:89–95

    PubMed  Article  Google Scholar 

  • van Haarst AD, Oitzl MS, de Kloet ER (1997) Facilitation of feedback inhibition through blockade of glucocorticoid receptors in the hippocampus. Neurochem Res 22:1323–1328

    PubMed  Article  Google Scholar 

  • Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51:32–58

    PubMed  CAS  Article  Google Scholar 

  • Wang CC, Wang SJ (2009) Modulation of presynaptic glucocorticoid receptors on glutamate release from rat hippocampal nerve terminals. Synapse 63:745–751

    PubMed  CAS  Article  Google Scholar 

  • Xu Y, Day TA, Buller KM (1999) The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta administration. Neuroscience 94:175–183

    PubMed  CAS  Article  Google Scholar 

  • Yehuda R, LeDoux J (2007) Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 56:19–32

    PubMed  CAS  Article  Google Scholar 

  • Yehuda R, Seckl J (2011) Minireview: stress-related psychiatric disorders with low cortisol levels: a metabolic hypothesis. Endocrinology 152:4496–4503

    PubMed  CAS  Article  Google Scholar 

  • Yehuda R, Halligan SL, Golier JA, Grossman R, Bierer LM (2004) Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology 29:389–404

    PubMed  CAS  Article  Google Scholar 

  • Yehuda R, Bierer LM, Andrew R, Schmeidler J, Seckl JR (2009) Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors. J Psychiatr Res 43:877–883

    PubMed  Article  Google Scholar 

  • Zhang ZH, Felder RB (2004) Melanocortin receptors mediate the excitatory effects of blood-borne murine leptin on hypothalamic paraventricular neurons in rat. Am J Physiol Regul Integr Comp Physiol 286:R303–R310

    PubMed  CAS  Article  Google Scholar 

  • Zhang R, Packard BA, Tauchi M, D’Alessio DA, Herman JP (2009) Glucocorticoid regulation of preproglucagon transcription and RNA stability during stress. Proc Natl Acad Sci USA 106:5913–5918

    PubMed  CAS  Article  Google Scholar 

  • Ziegler DR, Herman JP (2000) Local integration of glutamate signaling in the hypothalamic paraventricular region: regulation of glucocorticoid stress responses. Endocrinology 141:4801–4804

    PubMed  CAS  Article  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge support from NIH grants DK059803 (BM), NS007453 (JMM), MH049698, MH069725, MH069860, and MH090574 (JPH). We are also grateful for the artistic contributions of Anne Christiansen and Nathan Evanson.

Author information

Affiliations

  1. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Metabolic Diseases Institute, 2170 E. Galbraith Rd, Cincinnati, OH, 45237-0506, USA

    Brent Myers, Jessica M. McKlveen & James P. Herman

Authors
  1. Brent Myers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jessica M. McKlveen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James P. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brent Myers.

Additional information

Special Issue on Stress (Kvetnansky and Saavedra, Editors).

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Myers, B., McKlveen, J.M. & Herman, J.P. Neural Regulation of the Stress Response: The Many Faces of Feedback. Cell Mol Neurobiol 32, 683–694 (2012). https://doi.org/10.1007/s10571-012-9801-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-012-9801-y

Keywords

  • Hypothalamo–pituitary–adrenocortical axis
  • Corticotropin-releasing hormone
  • Corticosterone
  • Glucocorticoid receptor
  • Hypothalamus
  • Amygdala
  • Prefrontal cortex