DETERMINATION OF THE DETAILED HYPOTHALAMIC ROUTE OF THE MILK-EJECTION REFLEX IN THE GUINEA-PIG

Abstract

SUMMARY The effect of various types of surgical damage to the forebrain on the release of oxytocin in response to electrical stimulation of the discrete ascending milk-ejection reflex pathway in the mid-brain was investigated in 99 anaesthetized lactating guinea-pigs. Oxytocin release was measured by comparison of experimental milk-ejection responses with the response to i.v. injection of known amounts of synthetic oxytocin. Removal of the entire telencephalon, including cerebral cortex, hippocampi, amygdalae and forebrain rostral to the hypothalamus, did not affect the subsequent release of oxytocin after electrical stimulation of the pathway in the mid-brain, from which it was concluded that the reflex pathway within the forebrain is entirely diencephalic. Transection of the hypothalamus immediately rostral to the paraventricular (PV) nuclei was without effect, while transection immediately caudal to the PV nuclei blocked the release of oxytocin. Destruction of the PV nuclei by a radiofrequency lesion which spared the supraoptic (SO) nuclei blocked the release of oxytocin. Undercutting both PV nuclei so as to isolate them from the ventral hypothalamus blocked the release of oxytocin. Undercutting the PV nucleus ipsilateral to the stimulated side of the mid-brain blocked the release of oxytocin, while undercutting the contralateral PV nucleus had no effect. The PV nuclei, therefore, lie on the ascending path of the milk-ejection reflex, the SO nuclei do not, and, from the mid-brain forwards, the ascending pathway remains uncrossed. The course of the reflex pathway was traced rostrally from the mesodiencephalic junction by making narrow transverse knife-cuts and determining which cuts reduced or blocked the release of oxytocin after mid-brain stimulation. At this level, the pathway on each side of the brain is represented by separate dorsal and ventral paths and in the present study it was found that the ventral path is more important than the dorsal path in terms of oxytocin release. The ventral path passes forward in the medial forebrain bundle, in the far-lateral hypothalamus, while the dorsal path enters the posterior hypothalamus dorsally in the periventricular region at the top of the third ventricle and impinges on the thalamic reuniens nucleus. Shortly afterwards the dorsal path swings abruptly in the lateral direction to join the ventral path in the lateral hypothalamus. The reunited pathway then moves forward in this position until it is level with the PV nuclei, where it swings dorsomedially to relay with the lateral tip of the ipsilateral PV nucleus, and in doing so intermingles with the descending neurosecretory fibres from this nucleus.