EVIDENCE FOR A HYPOTHALAMIC OXYTOCIN-SENSITIVE PATTERN-GENERATING NETWORK GOVERNING OXYTOCIN NEURONS IN-VITRO

During lactation and parturition, magnocellular oxytocin (OT) neurons display a characteristic bursting electrical activity responsible for pulsatile OT release. We investigated this activity using hypothalamic organotypic slice cultures enriched in magnocellular OT neurons. As s hown here, the neurons are functional and actively secrete amidated OT into the cultures. Intracellular recordings were made from 23 spontan eously bursting and 28 slow irregular neurons, all identified as oxyto cinergic with biocytin and immunocytochemistry. The bursting electrica l activity was similar to that described in vivo and was characterized by bursts of action potentials (20.1 +/- 4.3 Hz) lasting similar to 6 sec, over an irregular background activity. OT (0.1-1 mu M), added to the medium, increased burst frequency, reducing interburst intervals by 70%. The peptide also triggered bursting in 27% of nonbursting neur ons. These effects were mimicked by the oxytocin receptor (OTR) agonis t [Thr(4), Gly(7)]-OT and inhibited by the OTR antagonist desGly-NH(2) d(CH2)(5)[D-Tyr(2), Thr(4)]OVT. Burst rhythmicity was independent of m embrane potential. Hyperpolarization of the cells unmasked volleys of afferent EPSPs underlying the bursts, which were blocked by CNQX, an A MPA/kainate receptor antagonist. Our results reveal that OT neurons ar e part of a hypothalamic rhythmic network in which a glutamatergic inp ut governs burst generation. OT neurons, in turn, exert a positive fee dback on their afferent drive through the release of OT.