Anatomical and functional demonstration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway

TLDR

Mounting evidence indicates the suprachiasmatic nucleus (SCN) directly influences adrenal cortex sensitivity to ACTH. This study investigated anatomical and functional connections between the SCN and the adrenal gland. Transneuronal tracing revealed a multisynaptic SCN–adrenal pathway via vasopressin/VIP efferents to paraventricular autonomic neurons and spinal cord, and light exposure caused a rapid, ACTH‑independent drop in corticosterone in intact animals, indicating direct SCN regulation of adrenal activity.

Abstract

Abstract In view of mounting evidence that the suprachiasmatic nucleus (SCN) is directly involved in the setting of sensitivity of the adrenal cortex to ACTH, the present study investigated possible anatomical and functional connections between SCN and adrenal. Transneuronal virus tracing from the adrenal revealed first order labelling in neurons in the intermedio‐lateral column of the spinal cord that were shown to receive an input from oxytocin fibres and subsequently second‐order labelling in neurons of the autonomic division of the paraventricular nucleus. The latter neurons were shown to receive an input from vasopressin or vasoactive intestinal peptide (VIP) containing SCN efferents. The true character of this SCN input to second‐order neurons was also demonstrated by the fact that third‐order labelling was present within the SCN, vasopressin or VIP neurons. The functional presence of the SCN–adrenal connection was demonstrated by a light‐induced fast decrease in plasma corticosterone that could not be attributed to a decrease in ACTH. Using intact and SCN‐lesioned animals, the immediate decrease in plasma corticosterone was only observed in intact animals and only at the beginning of the dark period. This fast decrease of corticosterone was accompanied by constant basal levels of blood adrenaline and noradrenaline, and is proposed to be due to a direct inhibition of the neuronal output to the adrenal cortex by light‐mediated activation of SCN neurons. As a consequence, it is proposed that the SCN utilizes neuronal pathways to spread its time of the day message, not only to the pineal, but also to other organs, including the adrenal, utilizing the autonomic nervous system.