Parallel trajectories in the discovery of the SCN-OVLT and pituitary portal pathways: Legacies of Geoffrey Harris.

A map of central nervous system organization based on vascular networks provides a layer of organization distinct from familiar neural networks or connectomes. As a well-established example, the capillary networks of the pituitary portal system enable a route for small amounts of neurochemical signals to reach local targets by traveling along specialized pathways, thereby avoiding dilution in the systemic circulation. The first evidence of such a pathway in the brain came from anatomical studies identifying a portal pathway linking the hypothalamus and the pituitary gland. Almost a century later, we demonstrated a vascular portal pathway that joined the capillary beds of the suprachiasmatic nucleus and a circumventricular organ, the organum vasculosum of the lamina terminalis, in a mouse brain. For each of these portal pathways, the anatomical findings opened many new lines of inquiry, including the determination of the direction of flow of information, the identity of the signal that flowed along this pathway, and the function of the signals that linked the two regions. Here, we review landmark steps to these discoveries and highlight the experiments that reveal the significance of portal pathways and more generally, the implications of morphologically distinct nuclei sharing capillary beds.