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Abstract
BackgroundIncreased 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.ResultsGramicidin-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.ConclusionWe 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.
Highlights
GABA, a major neurotransmitter in the mammalian central nervous system (CNS), acts through ionotropic GABAA/GABAC or metabotropic GABAB receptors [1]
We obtained evidence that the inhibitory-to-excitatory switch in GABAergic transmission is reversed after the cessation of lactation
We provided neurophysiological evidence that the up-regulation of Na+-K+-2Cl− cotransporter isotype 1 (NKCC1) and the down-regulation of K+-Cl− cotransporter isotype 2 (KCC2) are responsible for the depolarizing shift of Reversal potential of GABAA receptor-mediated response (EGABA) and the resultant emergence of GABAergic excitation in the magnocellular neurosecretory cells (MNCs) of multiparous lactating rats
Summary
GABA, a major neurotransmitter in the mammalian central nervous system (CNS), acts through ionotropic GABAA/GABAC or metabotropic GABAB receptors [1]. We have found that in the magnocellular neurosecretory cells (MNCs) of the paraventricular (PVN) and supraoptic nuclei (SON) of the rat, GABAergic inhibition is converted into excitation in a reversible fashion in response to chronic hyperosmotic stress given by 2 % NaCl as drinking solution This switch enhances the secretion of the antidiuretic hormone argininevasopressin (AVP) and the natriuretic hormone oxytocin from these neurons [12]. If such a change occurs, the secretion of oxytocin, a neurohormone with milk-ejecting function in lactating mammals [13], and AVP, another neurohormone which helps to prevent the mother from being dehydrated during lactation and maintain milk yield [14,15,16], would significantly increase, considering that the output of MNCs is regulated by the dense GABAergic innervation [17] In testing this hypothesis, we utilized female rats in four conditions: 1) virgin, 2) lactating after giving the first successful birth (Lac1), 3) lactating after giving birth 3 times (Lac3) and 4) in dry period after giving birth 3 times (Dry). We sought to test the hypothesis that the GABAA receptor-mediated inhibition of MNCs is altered in lactating rats
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