Chapter 4.1 Neurocircuit regulation of the hypothalamo-pituitary-adrenocortical stress response — an overview

Abstract

Abstract: Central integration of the hypothalamo–pituitary–adrenocortical (HPA) axis stress response is controlled by neurosecretory neurons in the medial parvocellular paraventricular nucleus (PVN). Activation of the PVN is a complex process regulated by both direct and indirect neuronal connections, as well as communication with blood-borne messengers. Ascending brainstem pathways from the nucleus of the solitary tract (both catecholaminergic and noncatecholaminergic systems) and serotonergic midbrain raphe nuclei provide direct neuronal excitation of PVN neurons. Stimulation of the HPA axis is also mediated by transsynaptic inputs from the medial and central amygdaloid nuclei, which disinhibit the PVN by way of GABAergic relay neurons in the hypothalamus and bed nucleus of the stria terminalis (BST), and perhaps enhance excitatory input from the brainstem. Inhibition of the HPA axis is controlled by PVN-projecting GABA neurons in the hypothalamus and BST, which are driven in part by descending stimulatory inputs from ventral subiculum and infralimbic cortex. The PVN is profoundly affected by blood-borne factors (including peptides and cytokines); these messengers communicate with the PVN through interactions with circumventricular organs or by induction of perivascular prostaglandin synthesis. Finally, glucocorticoids can directly inhibit PVN neurons, by diffusion from the dense vascular beds localized in this region. Thus, activation of the HPA axis is controlled by a wide variety of signals from both brain and periphery, which are thence effectively integrated into a net secretory signal at the level of the hypophysiotrophic PVN neuron.