Action of endogenous oxytocin within the paraventricular or supraoptic nuclei: A powerful link in the regulation of the bursting pattern of oxytocin neurons during the milk-ejection reflex in rats

Abstract

During suckling, the periodic and synchronous bursting activity of oxytocin neurons has been shown to be facilitated by oxytocin itself, acting via several target sites, including the magnocellular nuclei. To investigate the role of the endogenous oxytocin released within the magnocellular nuclei during the milk-ejection reflex in the rat, an oxytocin antagonist (50 μM solution of [d(CH 2) 5,Tyr(Me) 2,Orn 8]-vaso-tocin) was pressure-injected into either one paraventricular or one supraoptic nucleus while recording the bursting pattern of oxytocin neurons within the injected nucleus and within a contralateral nucleus. The oxytocin antagonist was injected either during an ongoing milk-ejection reflex or during its facilitation induced by oxytocin (1 μ1 of 1 μM solution injected into the third ventricle, i.e. 1 ng). During an ongoing milk-ejection reflex, injections of the oxytocin antagonist (10 nl of 50 μM solution, i.e. 50 ng) into the paraventricular or supraoptic nucleus decreased (more than 20% change) the burst amplitude (total number of spikes/burst) of neurons within the injected nucleus in 100% of tests, and simultaneously of contralateral neurons in 68% of tests. Burst periodicity of the entire population was also decreased in 50% of tests whatever the nucleus injected, but burst desynchronization was never observed. Successive injections of minute volumes of oxytocin (10 nl of 10 μM solution, i.e. 0.1 ng) into the paraventricular or supraoptic nucleus (which will progressively affect a greater number of neurons) first increased burst amplitude of oxytocin neurons within the injected nucleus and then increased simultaneously burst amplitude of contralateral neurons and burst frequency of the whole oxytocin neuron population. All these results suggest that the recruitment of a critical number of oxytocin neurons within one nucleus induces changes in the bursting activity of the oxytocin neurons in the four magnocellular nuclei. Within the minute following an intracerebroventricular oxytocin injection, the oxytocin antagonist injected into the supraoptic nucleus not only prevented the oxytocin-induced facilitation but also completely interrupted the milk-ejection reflex. When injected into the paraventricular nucleus, the oxytocin antagonist was less efficient: it decreased the oxytocin-induced facilitation but the reflex was not blocked. Similar partial inhibitory effect (decrease in burst amplitude and burst frequency) was also observed when the oxytocin antagonist was injected into the supraoptic nucleus after facilitation of the milk-ejection reflex by intracerebroventricular oxytocin injection. In conclusion, endogenous oxytocin released within the magnocellular nuclei during suckling represents a necessary link of the neuronal network regulating the bursting activity of oxytocin neurons. Intranuclear oxytocin regulates locally the burst amplitude of oxytocin neurons and their excitability which in turn will influence the bursting pattern of the whole oxytocin neuron population.