Arginine Vasopressin-Containing Neurons of the Suprachiasmatic Nucleus Project to CSF

Abstract

Arginine vasopressin (AVP) expressing neurons form the major population in the brain’s circadian clock located in the hypothalamic suprachiasmatic nucleus (SCN). They participate in inter-neuronal coupling and provide an output signal for synchronizing daily rhythms. AVP is present at high concentrations in the CSF and fluctuates on a circadian timescale. While it is assumed that rhythms in CSF AVP are of SCN origin, a route of communication between these compartments has not been delineated. Using immunochemistry and cell filling techniques, we determine the morphology and location of AVP neurons in mouse and delineate their axonal and dendritic processes. Cholera toxin β subunit (CTβ) tracer injected into the lateral ventricle tests whether AVP neurons communicate with CSF. Most importantly, the results indicate that AVP neurons lie in close proximity to the 3^rd ventricle, and their processes cross the ventricular wall into the CSF. We also report that contrary to widely held assumptions, AVP neurons do not fully delineate the SCN borders as PER2 expression extends beyond the AVP region. AVP neurons form a rostral prong originating in the SCN medial- and ventral-most aspect. AVP is lacking in the mid-dorsal shell but does occur at the base of the SCN just above the optic tract. Finally, neurons of the rostral SCN are smaller than those lying caudally. These findings extend our understanding of AVP signaling potential, demonstrate the heterogeneity of AVP neurons, and highlight limits in using this peptide to delineate the mouse SCN.

Significance Statement There is a high amplitude circadian rhythm of arginine vasopressin (AVP) in the cerebroventricular fluid (CSF), presumed to be of suprachiasmatic nucleus (SCN) origin. There is however, no known route of communication between these compartments. We demonstrate that in the mouse SCN, processes of AVP neurons course toward the 3rd ventricle and cross the ventricular wall to reach the CSF, thereby enabling vasopressinergic signals to reach many brain regions bearing receptors for this peptide. Also, the SCN extends beyond the borders delineated by AVP neurons and rostral AVP neurons are smaller than caudal populations. The work extends our understanding of AVP signaling potential, the heterogeneity of AVP neurons, and highlights limits in using this peptide to delineate the SCN.