Plasticity in GABA_AReceptor Subunit mRNA Expression by Hypothalamic Magnocellular Neurons in the Adult Rat

Abstract

The magnocellular hypothalamic neurons exhibit a substantial degree of structural and functional plasticity over the time of pregnancy, parturition, and lactation. This study has used in situ hybridization techniques to examine whether the content of ␣ 1 , ␣ 2 , ␤ 2 , and ␥ 2 GABA A receptor subunit mRNAs expressed by these cells fluctuates over this period. A process of regional, followed by cellular and then topographical, analyses within the supraoptic (SON) and posterior paraventricular (PVN) nuclei revealed that an increase in magnocellular ␣ 1 subunit mRNA content occurred during the course of pregnancy up to day 19, after which a decline in expression was detected on the day of parturition. Significant fluctuations of this nature were observed only in the oxytocin neuron-enriched regions of the SON and PVN. The expression of ␣ 2 , ␤ 2 , and ␥ 2 subunit mRNAs in the SON and PVN and of all subunit mRNAs in the cingulate cortex did not change over this period. During lactation, ␥ 2 subunit mRNA content within the PVN increased significantly on day 14 of lactation as compared with day 7, and topographical analysis suggested that it involved principally magnocellular vasopressin neurons.These results demonstrate the cell-and subunit-specific regulation of GABA A receptor mRNA expression within the hypothalamic magnocellular system. In particular, they suggest that fluctuations in ␣ 1 subunit expression may contribute to the marked variations in electrical activity exhibited by magnocellular oxytocin neurons at the time of parturition. More generally, they provide evidence in support of GABA A receptor plasticity within a physiological context in the adult rat brain.

Changes in Expression and Function of Extrasynaptic GABAAReceptors in the Rat Hippocampus during Pregnancy and after Delivery

“…Late pregnancy was also associated with an increase in the abundance of the ␣ 1 subunit mRNA in oxytocin neurons of the supraoptic nucleus of the hypothalamus (Fénelon and Herbison, 1996). Our present immunohistochemical data confirm our previous observation of the downregulation of ␥ 2 subunit expression in the hippocampus of rats during pregnancy.…”

Progesterone-metabolite prevents protein kinase C-dependent modulation of gamma -aminobutyric acid type A receptors in oxytocin neurons

“…Our findings do not necessarily demonstrate that direct phosphorylation of GABA A receptors by PKC is prevented; however, several phosphorylation sites are present at the ␥2 and the ␤2 subunit (12, 13), both of which are expressed in the SON (see ref. 14). Furthermore activation of PKC has variable effects on GABA A receptor activity (15)(16)(17)(18), which are likely to be caused by cell-specific differentiation in GABA A receptor subunit composition.…”

Pregnancy and the endocrine regulation of the baroreceptor reflex

“…Expression of different GABA A receptor subunits varies between brain regions and even cell types within a region (133) and can be differentially regulated by numerous factors, including neuronal activity (174), and the ovarian hormones estrogen (39,172) and progesterone (60,136,140,172,174). It was previously reported that GABA A receptors with a higher proportion of ␣ 1 -compared with ␣ 2 -receptor subunits were most sensitive to neurosteroid modulation (153), and expression of the ␣ 1 -subunit is increased in hypothalamic oxytocin neurons in late pregnancy (31,59). In the RVLM, expression of the ␣ 1 -subunit is several hundred times greater than expression of the ␣ 2 -subunit, suggesting that GABA A receptors in this region should be sensitive to neuro- Fig.…”