Physiological activation of the magnocellular hypothalamo-neurohypophysial system induces a coordinated astrocytic withdrawal from between the magnocellular somata and the parallel-projecting dendrites of the supraoptic nucleus. Neural lobe astrocytes release engulfed axons and retract from their usual positions along the basal lamina. Occurring on a minutes-to-hours time scale, these changes are accompanied by increased direct apposition of both somatic and dendritic membrane, the formation of dendritic bundles, the appearance of novel multiple synapses in both the somatic and dendritic zones, and increased neural occupation of the perivascular basal lamina. Reversal, albeit with varying time courses, is achieved by removing the activating stimuli. Additionally, activation results in interneuronal coupling increases that are capable of being modulated synaptically via second messenger-dependent mechanisms. These changes appear to play important roles in control and coordination of oxytocin and vasopressin release during such conditions as lactation and dehydration.