Schematic representation of the hypothalamo-pituitary-adrenal (HPA) axis and its neuronal inputs. Corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-expressing parvocellular neurons in the paraventricular nucleus (PVN) project to pituitary (via the median eminence) where they stimulate adrenocorticotrophic hormone (ACTH) synthesis and secretion, subsequently triggering corticosteroid synthesis and release from the adrenal cortex. Besides acting in the brain to regulate various behaviours, corticosteroids fine-tune the subsequent pattern (amplitude and duration) of corticosteroid secretion; they activate their cognate receptors in the pituitary, hypothalamus and hippocampus and bed nucleus of the stria terminalis (BNST, a relay between the hippocampus/amygdala and the PVN) to restrain, and in the amygdala to enhance, adrenocortical secretion. Monoaminergic transmitters, namely, norepinephrine, serotonin and dopamine released from midbrain nuclei (the locus coeruleus [LC], raphé and ventral tegmental area [VTA] and substantia nigra [SN], respectively) exert modulatory effects on all brain regions involved in the control of the HPA axis. 'Plus' signs (green) indicate positive drive on the HPA axis; 'minus' signs (red) represent sites of corticosteroid negative feedback; 'clock' signs denote neuronal populations known to respond rapidly to corticosteroids. Corticosteroids are secreted rhythmically, displaying ultradian and circadian patterns. The circadian peak coincides with the onset of the daily activity cycle (dark phase in rodents, light phase in humans). While the physiological and behavioural significance of the ultradian rhythms of corticosteroid secretion is still unclear, it is plausible that they serve to dynamically fine-tune the regulation of the HPA axis and thus, to facilitate adaptive processes. LD, light-dark cycle.