The DOI matches its Crossref record.
The Role of the Hippocampus in Feedback Regulation of the Hypothalamic-Pituitary-Adrenocortical Axis*
Abstract
There is considerable, although not entirely consistent, evidence that the hippocampus inhibits most aspects of HPA activity, including basal (circadian nadir) and circadian peak secretion as well as the onset and termination of responses to stress. Although much of the evidence for these effects rests only on the measurement of corticosteroids, recent lesion and implant studies indicate that the hippocampus regulates adrenocortical activity at the hypothalamic level, via the expression and secretion of ACTH secretagogues. Such inhibition results largely from the mediation of corticosteroid feedback, although more work is required to determine whether the hippocampus supplies a tonic inhibitory input in the absence of corticosteroids. It must be noted that the hippocampus is not the only feedback site in the adrenocortical system, since removal of its input only reduces, but does not abolish, the efficacy of corticosteroid inhibition, and since other elements of the axis appear eventually to compensate for deficits in feedback regulation. The importance of other feedback sites is further suggested not only by the presence of corticosteroid receptors in other parts of the brain and pituitary, but also by the improved prediction of CRF levels by combined hypothalamic and hippocampal receptor occupancy. The likelihood of feedback mediated by nonhippocampal sites underscores the need for future work to characterize hippocampal influence on HPA activity in the absence of changes i…
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“levels of glucocorticoids are regulated via negative feedback loops at several levels of the axis including the hippocampus and PFC (Diorio et al., 1993, Jacobson and Sapolsky, 1991).”
From The impact of developmental timing for stress and recovery (2015) · cites this paper as Jacobson and Sapolsky, 1991
In the citing paper
“Thus, GC measures can be an accurate indicator of stress response in vertebrates, once basal and stress-response measures can be differentiated (Jacobson and Sapolsky, 1991).”
From Glutamate receptors in domestication and modern human evolution (2020) · cites this paper as Jacobson and Sapolsky, 1991
Citations
Cited by
Sorted by citations
Items 101–171 of 171
Zijlmans, M. A. C., Riksen-Walraven, J. M., & de Weerth, C. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.02.015 · Cited by 221
Decreased hippocampal volume in healthy girls at risk of depression
Chen, M. C., Hamilton, J. P., & Gotlib, I. H. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.202 · Cited by 220
Role of adult hippocampal neurogenesis in stress resilience
Levone, B. R., Cryan, J. F., & O'Leary, O. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.11.003 · Cited by 218
Pagliaccio, D., Luby, J. L., Bogdan, R., Agrawal, A., Gaffrey, M. S., Belden, A. C., Botteron, K. N., Harms, M. P., & Barch, D. M. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2013.327 · Cited by 205
Circadian regulation of cortisol after hippocampal damage in humans
Buchanan, T. W., Kern, S., Allen, J. S., Tranel, D., & Kirschbaum, C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.08.014 · Cited by 206
Wood, G. E., Beylin, A. V., & Shors, T. J. (2001) · Behavioral Neuroscience · doi:10.1037/0735-7044.115.1.175 · Cited by 198
Forray, M. I., & Gysling, K. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.07.011 · Cited by 191
A physiologic approach to diagnosis of the Cushing syndrome.
Raff, H., & Findling, J. W. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-138-12-200306170-00010 · Cited by 186
Alt, S. R., Turner, J. D., Klok, M. D., Meijer, O. C., Lakke, E. A. J. F., DeRijk, R. H., & Muller, C. P. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.09.001 · Cited by 184
The neurobiology and neuroendocrinology of stress
McEwen, B. S. (2002) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(01)00009-0 · Cited by 184
Miklós, I. H., & Kovács, K. J. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00147-1 · Cited by 182
Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine
McEwen, B. S., & Chattarji, S. (2004) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2004.09.008 · Cited by 174
Memory consolidation in human sleep depends on inhibition of glucocorticoid release
Plihal, W., & Born, J. (1999) · NeuroReport · doi:10.1097/00001756-199909090-00009 · Cited by 171
Quirin, M., Pruessner, J. C., & Kuhl, J. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.01.013 · Cited by 167
Obese men respond to cognitive but not to catabolic brain insulin signaling
Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W. (2008) · International Journal of Obesity · doi:10.1038/sj.ijo.0803722 · Cited by 165
Circuit and molecular architecture of a ventral hippocampal network
Gergues, M. M., Han, K. J., Choi, H. S., Brown, B., Clausing, K. J., Turner, V. S., Vainchtein, I. D., Molofsky, A. V., & Kheirbek, M. A. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0705-8 · Cited by 158
Hsu, D. T., Chen, F.-L., Takahashi, L. K., & Kalin, N. H. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00032-8 · Cited by 154
Kandola, A., Hendrikse, J., Lucassen, P. J., & Yücel, M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00373 · Cited by 155
Altered Stress-Induced Anxiety in Adenylyl Cyclase Type VIII-Deficient Mice
Schaefer, M. L., Wong, S. T., Wozniak, D. F., Muglia, L. M., Liauw, J. A., Zhuo, M., Nardi, A., Hartman, R. E., Vogt, S. K., Luedke, C. E., et al. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-13-04809.2000 · Cited by 152
Pruessner, M., Pruessner, J. C., Hellhammer, D. H., Bruce Pike, G., & Lupien, S. J. (2007) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2006.12.007 · Cited by 150
Silvers, J. A., Lumian, D. S., Gabard-Durnam, L., Gee, D. G., Goff, B., Fareri, D. S., Caldera, C., Flannery, J., Telzer, E. H., Humphreys, K. L., et al. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.0038-16.2016 · Cited by 140
Glucocorticoid receptor protein expression in human hippocampus; stability with age
Wang, Q., Van Heerikhuize, J., Aronica, E., Kawata, M., Seress, L., Joels, M., Swaab, D. F., & Lucassen, P. J. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.019 · Cited by 144
Geerlings, M. I., & Gerritsen, L. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.12.032 · Cited by 138
Domes, G., Heinrichs, M., Reichwald, U., & Hautzinger, M. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00085-3 · Cited by 135
Gerritsen, L., Comijs, H. C., van der Graaf, Y., Knoops, A. J. G., Penninx, B. W. J. H., & Geerlings, M. I. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.029 · Cited by 132
Hypothalamic-pituitary – adrenal axis-feedback control
Keller‐Wood, M. (2015) · Comprehensive Physiology · doi:10.1002/cphy.c140065 · Cited by 131
Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease
Craig, C. F., Filippone, R. T., Stavely, R., Bornstein, J. C., Apostolopoulos, V., & Nurgali, K. (2022) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02354-1 · Cited by 124
Plasma Cortisol and Progression of Dementia in Subjects With Alzheimer-Type Dementia
Csernansky, J. G., Dong, H., Fagan, A. M., Wang, L., Xiong, C., Holtzman, D. M., & Morris, J. C. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.12.2164 · Cited by 426
Jaferi, A., & Bhatnagar, S. (2006) · Endocrinology · doi:10.1210/en.2005-1393 · Cited by 122
Hartmann, J., Bajaj, T., Klengel, C., Chatzinakos, C., Ebert, T., Dedic, N., McCullough, K. M., Lardenoije, R., Joëls, M., Meijer, O. C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109185 · Cited by 119
Neural mechanisms underlying heterogeneity in the presentation of anxious temperament
Shackman, A. J., Fox, A. S., Oler, J. A., Shelton, S. E., Davidson, R. J., & Kalin, N. H. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214364110 · Cited by 113
Modulation of binding sites for corticotropin-releasing hormone by chronic psychosocial stress
Fuchs, E., & Flügge, G. (1995) · Psychoneuroendocrinology · doi:10.1016/0306-4530(94)e0006-u · Cited by 118
Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1377 · Cited by 117
Delgado y Palacios, R., Campo, A., Henningsen, K., Verhoye, M., Poot, D., Dijkstra, J., Van Audekerke, J., Benveniste, H., Sijbers, J., Wiborg, O., et al. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.05.014 · Cited by 113
Warne, J. P. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.09.036 · Cited by 112
Genetic approaches to hypothalamic-pituitary-adrenal axis regulation
Arnett, M. G., Muglia, L. M., Laryea, G., & Muglia, L. J. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.215 · Cited by 105
Rapid treatment-induced brain changes in pediatric CRPS
Erpelding, N., Simons, L., Lebel, A., Serrano, P., Pielech, M., Prabhu, S., Becerra, L., & Borsook, D. (2016) · Brain Structure and Function · doi:10.1007/s00429-014-0957-8 · Cited by 108
MacLullich, A. M. J., Ferguson, K. J., Wardlaw, J. M., Starr, J. M., Deary, I. J., & Seckl, J. R. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2610 · Cited by 100
Exercising our brains: how physical activity impacts synaptic plasticity in the dentate gyrus.
Christie, B. R., Eadie, B. D., Kannangara, T. S., Robillard, J. M., Shin, J., & Titterness, A. K. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8033-2 · Cited by 99
Nicotine modulation of fear memories and anxiety: Implications for learning and anxiety disorders
Kutlu, M. G., & Gould, T. J. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.07.029 · Cited by 97
Corticotropin-releasing factor induces social preferences in male prairie voles
DeVries, A. (2002) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(01)00073-7 · Cited by 97
Involvement of Brain-Derived Neurotrophic Factor in Late-Life Depression
Dwivedi, Y. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2012.10.026 · Cited by 86
McVey Neufeld, K.-A., Kay, S., & Bienenstock, J. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00294 · Cited by 79
Fruehwald-Schultes, B., Kern, W., Bong, W., Wellhoener, P., Kerner, W., Born, J., Fehm, H. L., & Peters, A. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.9.5953 · Cited by 75
Changes in Cortisol and Growth Hormone Secretion During Nocturnal Sleep in the Course of Aging
Kern, W., Dodt, C., Born, J., & Fehm, H. L. (1996) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/51a.1.m3 · Cited by 81
Stress and Mindfulness in Parkinson's Disease: Clinical Effects and Potential Underlying Mechanisms
van der Heide, A., Meinders, M. J., Speckens, A. E. M., Peerbolte, T. F., Bloem, B. R., & Helmich, R. C. (2021) · Movement Disorders · doi:10.1002/mds.28345 · Cited by 80
Adult attachment insecurity and hippocampal cell density
Quirin, M., Gillath, O., Pruessner, J. C., & Eggert, L. D. (2010) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsp042 · Cited by 71
Mechanisms of brain glucocorticoid resistance in stress-induced psychopathologies
Merkulov, V. M., Merkulova, T. I., & Bondar, N. P. (2017) · Biochemistry (Moscow) · doi:10.1134/s0006297917030142 · Cited by 65
Evidence of a corticotropin-releasing hormone pulse generator in the macaque hypothalamus
Mershon, J. L., Sehlhorst, C. S., Rebar, R. W., & Liu, J. H. (1992) · Endocrinology · doi:10.1210/endo.130.5.1572307 · Cited by 70
Hippocampal volume as marker of daily life stress sensitivity in psychosis
Collip, D., Habets, P., Marcelis, M., Gronenschild, E., Lataster, T., Lardinois, M., Nicolson, N. A., & Myin-Germeys, I. (2013) · Psychological Medicine · doi:10.1017/s003329171200219x · Cited by 60
Andersen, M., Vinther, F., & Ottesen, J. T. (2013) · Mathematical Biosciences · doi:10.1016/j.mbs.2013.08.010 · Cited by 56
Developmental underpinnings of differences in rodent novelty‐seeking and emotional reactivity
Clinton, S. M., Stead, J. D. H., Miller, S., Watson, S. J., & Akil, H. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07811.x · Cited by 58
“…the hippocampus detects novelty (Roullet & Lassalle, 1990; Lever et al., 2006; Jeewajee et al., 2008), regulates neural stress circuits (Sapolsky et al., 1984; Jacobson & Sapolsky, 1991) and controls fear and anxiety-like behavior (Gray, 1982; McNaughton & Gray, 2000; Bannerman et al., 2002).”
BackgroundResultProtective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice
Tian, X., Sun, L., Gou, L., Ling, X., Feng, Y., Wang, L., Yin, X., & Liu, Y. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.048 · Cited by 57
Arnaldo, I., Corcoran, A. W., Friston, K. J., & Ramstead, M. J. D. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104590 · Cited by 56
Zannas, A. S., McQuoid, D. R., Payne, M. E., Steffens, D. C., MacFall, J. R., Ashley-Koch, A., & Taylor, W. D. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.02.008 · Cited by 53
Glutamate receptors in domestication and modern human evolution
O’Rourke, T., & Boeckx, C. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.004 · Cited by 50
Walker, S. E., Papilloud, A., Huzard, D., & Sandi, C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.10.008 · Cited by 49
Central nervous system-acting drugs influencing hypothalamic-pituitary-adrenal axis function
Locatelli, V., Bresciani, E., Tamiazzo, L., & Torsello, A. (2010) · Endocrine development · doi:10.1159/000262533 · Cited by 48
Uysal, N. (2015) · Medical Science Monitor · doi:10.12659/msm.893159 · Cited by 44
Pathways for Contextual Memory: The Primate Hippocampal Pathway to Anterior Cingulate Cortex
Wang, J., John, Y., & Barbas, H. (2021) · Cerebral Cortex · doi:10.1093/cercor/bhaa333 · Cited by 39
Kim, J., Lei, Y., Lu, X.-Y., & Kim, C. S. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01682-9 · Cited by 33
“The hippocampus, which includes high amounts of mineralocorticoid receptor and GR, regulates HPA-axis activity among limbic brain structures [22].”
BackgroundTamano, H., Fukura, K., Suzuki, M., Sakamoto, K., Yokogoshi, H., & Takeda, A. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.02.005 · Cited by 33
Mathias, S. R., Knowles, E. E. M., Kent, J. W., McKay, D. R., Curran, J. E., de Almeida, M. A. A., Dyer, T. D., Göring, H. H. H., Olvera, R. L., Duggirala, R., et al. (2016) · Human Brain Mapping · doi:10.1002/hbm.23025 · Cited by 28
Little, K., Olsson, C. A., Whittle, S., Youssef, G. J., Byrne, M. L., Simmons, J. G., Yücel, M., Foley, D. L., & Allen, N. B. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.85 · Cited by 29
Sinha, S., Patro, N., Tiwari, P. K., & Patro, I. K. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104877 · Cited by 28
Ritze, Y., Kern, W., Ebner, E.-M., Jahn, S., Benedict, C., & Hallschmid, M. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00663 · Cited by 28
The hypothalamo–pituitary–adrenal axis in major affective disorder: a review
Christensen, M. V., & Kessing, L. V. (2001) · Nordic Journal of Psychiatry · doi:10.1080/080394801317080873 · Cited by 25
Takeda, A., Tamano, H., Suzuki, M., Sakamoto, K., Oku, N., & Yokogoshi, H. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9732-z · Cited by 25
Poland, R. E., Lutchmansingh, P., Au, D., Edelstein, M., Lydecker, S., Hsieh, C., & McCracken, J. T. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00318-1 · Cited by 16
Psychophysiological Methods for the Study of Developmental Psychopathology
Fox, N. A., Ashley Hane, A., & Pérez‐Edgar, K. (2015) · Developmental Psychopathology · doi:10.1002/9780470939390.ch9 · Cited by 16
Chang, S.-H., Chang, Y.-M., Chen, H.-Y., Shaw, F.-Z., & Shyu, B.-C. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100569 · Cited by 5
Metadata
- Authors
- JACOBSON, L., & SAPOLSKY, R.
- Affiliations
- Stanford University (US)
- Corresponding author
- JACOBSON, LAUREN
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 1991-05
- Volume
- 12
- Issue
- 2
- Pages
- 118-134
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W2060644077
- Cited by
- 1,739
- References
- 0
- Citations by year
- 2026: 24 · 2025: 22 · 2024: 59 · 2023: 46 · 2022: 63 · 2021: 44 · 2020: 59 · 2019: 45 · 2018: 43 · 2017: 68 · 2016: 55 · 2015: 62 · 2014: 59 · 2013: 67 · 2012: 70
- FWCI
- 12.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag006633-08, 5f32mh009796-02)
- National Institute on Aging (AG-06633)
- National Institute of Mental Health (MH-09796)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- hippocampus, hypothalamic-pituitary-adrenal axis, corticosteroid feedback, corticosteroid receptors, circadian rhythm, stress response, vasopressin, corticotropin-releasing factor, adrenocortical function, lesion studies, receptor occupancy
- MeSH terms
- Adrenal Cortex, Aging, Animals, Mental Disorders, Feedback, Hippocampus, Humans, Hypothalamus, Pituitary Gland
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
