Stress and the Hippocampus

Publication Type:



de Kloet, E.R.


The Clinical Neurobiology of the Hippocampus: An integrative view , Oxford University Press, Oxford (2012)



DOI Name (links to online publication)



hippocampus; stress; brain; development; behaviour; hormones; glucocorticoids; receptor polymorphisms; gene transcription; depression; ageing


Environmental stimuli perceived as stressors and processed in higher brain circuits including the hippocampus activate the release of several neuropeptides eventually leading to the secretion of adrenal cortisol which feeds back on the brain. To exert this feedback, the action of cortisol is mediated by nuclear receptors that operate as gene transcription factors but can also directly affect neurotransmission. There are two types of receptors, the mineralocorticoid (MR) and glucocorticoid receptors (GR). Both serve complementary as master switch in the control of neural network responses that facilitate the defence and recovery of homeostasis underlying behavioural adaptation. Imbalance in MR:GR driven pathways, caused either by genetic receptor variants or by experince-related factors, compromises processing of stressful information. Therapies are therefore envisioned to rebalance the stress system for protection, resilience or repair from damaging signalling pathways that can introduce a bias towards stress-related brain disease. In this chapter, the basal pulsatility and the stress-induced modes of operation of the hypothalamic–pituitary–adrenal axis are described. Further, central highlights of cortisol action are presented on different levels of biological complexity from emotions and cognitive performance to their molecular underpinnings. Next is a discussion on genetic receptor variants and the programming of brain and behaviour by early experience. A brief synthesis of cortisol actions for clinical neurobiology of the hippocampus and some thoughts on potential treatment strategies conclude the chapter.