A novel role of vasopressin in the brain: Modulation of activity-dependentwater flux in the neocortex

The brain contains an intrinsic vasopressin fiber system the function of wh ich is unknown. It has been demonstrated recently that astrocytes express h igh levels of a water channel, aquaporin-4 (AQP4). Because vasopressin is k nown to regulate aquaporin expression and translocation in kidney collectin g ducts and thereby control water reabsorption, we hypothesized that vasopr essin might serve a similar function in the brain. By recording intrinsic o ptical signals in an acute cortical slice preparation we showed that evoked neuronal activity generates a radial water flux in the neocortex. The rapi d onset and high capacity of this flux suggest that it is mediated through the AQP4-containing astrocytic syncytium that spans the entire thickness of the neocortical mantle. Vasopressin and vasopressin receptor V1a agonists were found to facilitate this flux. V1a antagonists blocked the facilitator y effect of vasopressin and reduced the water flux even in the absence of a ny exogenous agonist. V2 agonists or antagonists had no effect. These data suggest that vasopressin and V1a receptors play a crucial role in the regul ation of brain water and ion homeostasis, most probably by modulating aquap orin-mediated water flux through astrocyte plasma membranes.