Synchronization of oxytocin neurons in suckled rats: possible role of bilateral innervation of hypothalamic supraoptic nuclei by single medullary neurons

Abstract

We have previously shown that oxytocin neurons located in the four hypothalamic magnocellular nuclei display synchronous bursts of action potentials before each milk ejection. The mechanisms involved in such a synchronization have, however, not yet been elucidated. In this study, we test the hypothesis of an extranuclear synchronization arising from a common extrahypothalamic input innervating bilateral magnocellular nuclei. First, two different retrograde tracers were injected into the right and left supraoptic nuclei of rats that were fixed 5-7 days later. Each tracer labelled numerous neurons in various brain regions ipsilateral or contralateral to the injection site, but colocalization of the two tracers within the same cell body could only be detected bilaterally in neurons in the ventromedial regions of the medulla oblongata. The axonal projections of these medullary neurons were then visualized by the unilateral microinjection of an anterograde tracer (BDA) within the ventromedial medulla oblongata. BDA-labelled axons afferent to the hypothalamus were found to branch towards both supraoptic nuclei through medial portions of the optic chiasma. Finally, in anaesthetized lactating rats, surgical lesions were placed medially through the optic chiasma and the electrical activity of oxytocin neurons in bilateral supraoptic nuclei was pair-recorded during suckling. The incidence of synchronous bursts in oxytocin neurons located within bilateral supraoptic nuclei were dramatically altered only when the medial portions of the optic chiasma were totally lesioned. Taken together, these data suggest that medullary neurons afferent to bilateral supraoptic nuclei are involved in the recruitment and synchronization of bursting in oxytocin neurons during suckling.

Central Nervous System Control of Oxytocin Secretion during Lactation

“…Neurons in this region project both to the SON and PVN. 161 Moos et al 132 however, found that lactating rats suckling bilaterally, but with extensive hypothalamic hemisection, failed to show OT burst synchronization, and the bursting that was observed was dramatically reduced in amplitude compared to controls. This region is near what is commonly referred to as the SON perinuclear zone (PNZ), which also has documented projections to the SON (see Refs.…”

“…124,125 Synaptic adrenergic (or noradrenergic) profiles making contact with OT neurons have been observed. Li et al 131 found that suckling-induced c-Fos expression was prominent in the A1 and A6 cell groups but not in the NTS, whereas Moos et al 132 reported activation of both A1 and A2 cell groups in the medulla and found numerous noradrenergic neurons could be labeled that projected to the SON. 127 While it is unclear whether the CCK data suggesting a more viscerally related yet apparently specific involvement of the NTS in OT release is relevant to milk ejection, this area remains important for further study.…”

“…126 Another NTS potential peptide transmitter, activin, favors innervation of OT regions and has been implicated in OT release. However, Moos et al 132 further indicated that the only medullary cell group that projected bilaterally to the SON was a noncatecholaminergic group in the ventromedial region between A1 and the raphé obscurus. A large number of NTS catecholaminergic neurons projecting to the PVN or SON expressed c-Fos following peripheral CCK injection, 125,128 and the noradrenergic transmission during CCK activation is critical for magnocellular activation.…”

“…155,156 An additional hypothalamic area proffered to mediate activation of the SON and PVN during suckling is an area just dorsomedial to the optic chiasm. 132,160,161 For example, hypothalamic midline knife cuts prevent most OT neurons on the side ipsilateral to the nursing pups from expressing milk ejection bursts, whereas bilateral suckling, or placing pups on the contralateral side to nurse, produces relatively normal bursting, although burst amplitudes are reduced. 157 However, these projections appear largely ipsilateral, and there is no other indication of their importance to milk ejection.…”

Coordinated Synchronization in the Electrically Coupled Network of Terminal Nerve Gonadotropin-Releasing Hormone Neurons as Demonstrated by Double Patch-Clamp Study

“…As has been shown in the previous electrophysiological studies, the mechanism is known to work in the synchronization of the neurons in the inferior olive (27,28), the suprachiasmatic nucleus (29) and the locus coeruleus (14), etc. Also, the mechanism has been considered to underlie the synchronization of oxytocin neurons in the supraoptic nucleus (30,31). It should be noted that the gap junctions provide a major means by which the neurons are coordinated in most of the interconnected networks mentioned above.…”