stimulus |  |  |  |  |  |  | adrenal cortex
--- | --- | --- | --- | --- | --- | --- | ---
| amygdala | CRF | hypothalamus | CRF | pituitary | ACTH |
Key
| stimulates
| inhibits
| groups of glucocorticoid receptors
| groups of other receptors
| action potential
|  |  |  |  | cortisol
prefrontal cortex |  | hippocampus |  |  |

Information received through the senses (smell, sight, hearing, touch, taste) or even certain thoughts, can signify a situation of danger, fear or excitement. These stimulate the amygdala into action.

The adrenal cortex is the outer shell of the adrenal gland. The adrenal cortex secretes the hormone cortisol into the bloodstream when stimulated by the hormone ACTH which is released by the (anterior) pituitary gland.

The amygdala is concerned with emotion and motivation. It receives information on events in the world or on thoughts that signify the presence of threat or danger or the need for heightened action. The emotional information extracted by the amygdala is sent to other brain regions such as the hypothalamus, which it can influence with its assessments of the emotional relevance of the information it receives. The amygdala secretes CRF, corticotropin-releasing factor, to stimulate the hypothalamus.

Corticotropin-releasing factor or CRF can act as a neurotransmitter, for instance when released by the amygdala to stimulate the hypothalamus. When released into the blood, CRF acts as a hormone, e.g. it is released by the hypothalamus into the blood supply around the pituitary gland, stimulating the pituitary to release ACTH (adrenocorticotropic hormone) into the bloodstream.

The hypothalamus is located immediately below the thalamus and that is from where it derives its name, hypo means below. The hypothalamus is involved in emotional reactions. It has links to the pituitary gland, so that emotional reactions organised in the hypothalamus link to hormonal secretions from the pituitary gland. The hypothalamus is stimulated by the amygdala to produce CRF, corticotropin-releasing factor. This in turn stimulates the (anterior) pituitary gland.

Corticotropin-releasing factor or CRF can act as a neurotransmitter, for instance when released by the amygdala to stimulate the hypothalamus. When released into the blood, CRF acts as a hormone, e.g. it is released by the hypothalamus into the blood supply around the pituitary gland, stimulating the pituitary to release ACTH (adrenocorticotropic hormone) into the bloodstream.

The pituitary gland is a gland located at the base of the brain in close proximity to the hypothalamus. During the stress response, the (anterior) pituitary gland is stimulated by the hormone CRF (corticotropin-releasing factor), secreted by the hypothalamus. This causes it to secrete ACTH (adrenocorticotropic hormone) into the bloodstream. ACTH in turn stimulates the adrenal cortex.

ACTH or adrenocorticotropic hormone is released by the (anterior) pituitary gland in response to stimulation by corticotropin-releasing factor (CRF) released by the hypothalamus. ACTH acts on the adrenal cortex of the adrenal gland to promote release of corticosteroid hormones, such as cortisol (in humans) and corticosterone (in rats and mice) into the bloodstream.

The prefrontal cortex (PFC) carries glucocorticoid receptors and is involved in regulating the stress response, via its links to the hypothalamus. The constant barrage of glucocorticoids as a consequence of HPA overactivity during chronic stress is deleterious for these glucocorticoid receptors and for neurons in the PFC, making them more susceptible to damage or death.

The PFC plays a critical role in exerting conscious control over behaviour, thoughts or impulses, and hence in regulating mood states. It is involved in planning and organising behaviour, making judgments and decisions and in concentrating on the task in hand. Damage to the prefrontal cortex could thus have important psychological implications.

The hippocampus is part of the limbic system (Book 2, Chapter 1) that deals with emotional information in the brain. The hippocampus has close connections with the adjacent cortex. It is involved in organising memory storage in the cortex and retrieving memories stored in the cortex. It is crucial in the formation and storage of certain kinds of conscious memory - such as recollection of facts, associations and events, known as declarative memory.

The hippocampus contains high levels of glucocorticoid receptors, which make it more vulnerable to long-term stress than most other brain areas. Almost uniquely, the hippocampus is also an area of the brain where new neurons can be 'born' (a process known as neurogenesis). Stress, via the effects of glucocorticoid hormones, leads to a decline in hippocampal function, through some combination of decline in hippocampal neurogenesis and increase in the death of hippocampal neurons. Some symptoms of depression, such as memory impairments, may be linked to this kind of hippocampal damage, which could affect the ability to retrieve conscious memories or to form new ones.

Cortisol is a hormone released, if there is a stressor, in response to an elevation of adrenocorticotropic hormone (ACTH) produced by the (anterior) pituitary gland.

Cortisol and corticosterone (the rat equivalent of cortisol) are examples of corticosteroids. They are also called glucocorticoids as they affect glucose metabolism. They facilitate the release of energy reserves from fat cells, and from glucose stores in the liver, into the blood, making energy available for fight or flight. High doses of cortisol in conditions of chronic stress cause damage to cortisol receptors (glucorcorticoid receptors), and to neurons in the hippocampus and prefrontal cortex, making them more susceptible to cell damage or death. (One suggestion is that the constant action of glucocorticoids may deplete the energy reserves of neurons, making them more vulnerable to damage or death.) In conditions of chronic stress, there is also a lot of unused glucose and fatty material in the blood; the latter can lead to fatty deposits in the arteries and to cardiovascular diseases.