Vázquez-Sola Aitana, Torres-Torrelo Hortensia, Yagüe Josué García
Grupo de Neurofisiología Celular, Departamento de Ciencias Médicas Básicas, Facultad de Medicina, Instituto de Medicina Molecular Aplicada-Nemesio Díez (IMMA-ND), Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe s/n, Madrid, Spain.
Exp Physiol. 2025 Jun;110(6):888-898. doi: 10.1113/EP092439. Epub 2025 May 1.
The sex hormones progesterone (P) and oestrogen (E) reorganize GABAergic transmission in the prefrontal cortex (PFC) during the transition from childhood to adolescence, generating a new excitatory-inhibitory balance necessary for the computational capacity of the mature PFC. Little is known, however, about the hormone receptors involved or whether there are sex differences in the modulation of GABAergic transmission they exert. We hypothesize that P and E can rapidly (within minutes) modulate GABAergic currents through G protein-coupled receptors, namely membrane P receptors (mPRs) and the G protein-coupled E receptor (GPER), respectively, in PFC. First, we quantified the expression of P and E receptors in PFC using quantitative RT-PCR. Secondly, we recorded synaptic (phasic) and extrasynaptic (tonic) GABAergic currents in basal conditions and in response to the activation of mPRs and GPER using patch-clamp recordings in PFC neurons of prepubertal female and male mice. Expression levels of mPRs differed in the PFC of females and males, but no differences were found in the basal levels of phasic or tonic GABAergic currents between sexes. Interestingly, selective activation of mPRs increased tonic GABAergic transmission in males but not in females, and activation of GPER increased phasic GABAergic transmission only in males. We also demonstrated that GABAergic modulation exerted by mPRs and GPER was dependent on protein kinase A and C. This study sheds light on new mechanisms by which P and E can rapidly modulate GABAergic transmission in PFC neurons through the activation of mPRs and GPER.
在从童年到青春期的过渡阶段，性激素孕酮（P）和雌激素（E）会重新组织前额叶皮质（PFC）中的γ-氨基丁酸（GABA）能传递，形成成熟PFC计算能力所需的新的兴奋-抑制平衡。然而，对于所涉及的激素受体，或者它们对GABA能传递的调节是否存在性别差异，我们知之甚少。我们假设，P和E可以分别通过G蛋白偶联受体，即膜孕酮受体（mPRs）和G蛋白偶联雌激素受体（GPER），在数分钟内快速调节PFC中的GABA能电流。首先，我们使用定量逆转录聚合酶链反应（RT-PCR）对PFC中P和E受体的表达进行了定量。其次，我们在青春期前雌性和雄性小鼠的PFC神经元中，采用膜片钳记录技术，记录了基础状态下以及mPRs和GPER激活后的突触（相位性）和突触外（紧张性）GABA能电流。mPRs的表达水平在雌性和雄性的PFC中有所不同，但两性之间的相位性或紧张性GABA能电流的基础水平未发现差异。有趣的是，mPRs的选择性激活增加了雄性而非雌性的紧张性GABA能传递，而GPER的激活仅增加了雄性的相位性GABA能传递。我们还证明，mPRs和GPER所施加的GABA能调节依赖于蛋白激酶A和C。这项研究揭示了P和E通过激活mPRs和GPER快速调节PFC神经元中GABA能传递的新机制。
