GABAergic inhibition is weakened or converted into excitation in the oxytocin and vasopressin neurons of the lactating rat

Seung Won Lee, Young Beom Kim, Jeong Sook Kim, Woong Bin Kim, Yoon Sik Kim, Hee Chul Han, Christopher S. Colwell, Young Wuk Cho, Yang In Kim

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Increased secretion of oxytocin and arginine vasopressin (AVP) from hypothalamic magnocellular neurosecretory cells (MNCs) is a key physiological response to lactation. In the current study, we sought to test the hypothesis that the GABAA receptor-mediated inhibition of MNCs is altered in lactating rats. Results: Gramicidin-perforated recordings in the rat supraoptic nucleus (SON) slices revealed that the reversal potential of GABAA receptor-mediated response (EGABA) of MNCs was significantly depolarized in the lactating rats as compared to virgin animals. The depolarizing EGABA shift was much larger in rats in third, than first, lactation such that GABA exerted an excitatory, instead of inhibitory, effect in most of the MNCs of these multiparous rats. Immunohistochemical analyses confirmed that GABAergic excitation was found in both AVP and oxytocin neurons within the MNC population. Pharmacological experiments indicated that the up-regulation of the Cl- importer Na+-K+-2Cl- cotransporter isotype 1 and the down-regulation of the Cl- extruder K+-Cl- cotransporter isotype 2 were responsible for the depolarizing shift of EGABA and the resultant emergence of GABAergic excitation in the MNCs of the multiparous rats. Conclusion: We conclude that, in primiparous rats, the GABAergic inhibition of MNCs is weakened during the period of lactation while, in multiparous females, GABA becomes excitatory in a majority of the cells. This reproductive experience-dependent alteration of GABAergic transmission may help to increase the secretion of oxytocin and AVP during the period of lactation.

Original languageEnglish
Article number34
JournalMolecular brain
Volume8
DOIs
Publication statusPublished - 2015 May 28

Keywords

  • Electrophysiology
  • GABA
  • KCC2
  • Lactation
  • NKCC1
  • Oxytocin
  • Vasopressin

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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