Trujeque-Ramos Saraí, Castillo-Rolón Diego, Galarraga Elvira, Tapia Dagoberto, Arenas-López Gabina, Mihailescu Stefan, Hernández-López Salvador
Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de Mexico, Mexico City, Mexico.
Front Neurosci. 2018 May 31;12:345. doi: 10.3389/fnins.2018.00345. eCollection 2018.
Recent studies, have shown that insulin increases extrasynaptic GABA receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used electrophysiological, molecular, and immunocytochemical techniques to examine the effect of insulin on the extrasynaptic GABA receptor-mediated tonic currents in brain slices. We found that insulin (20-500 nM) increases GABA-mediated tonic currents. Our results suggest that insulin promotes the trafficking of extrasynaptic GABA receptors from the cytoplasm to the cell membrane. Western blot analysis and immunocytochemistry showed that PFC extrasynaptic GABA receptors contain α-5 and δ subunits. Insulin effect on tonic currents decreased the firing rate and neuronal excitability in layer 5-6 PFC cells. These effects of insulin were dependent on the activation of the PI3K enzyme, a key mediator of the insulin response within the brain. Taken together, these results suggest that insulin modulation of the GABA-mediated tonic currents can modify the activity of neural circuits within the PFC. These actions could help to explain the alterations of cognitive processes associated with changes in insulin signaling.
最近的研究表明，胰岛素可增加海马体中突触外GABA受体介导的电流，从而引起神经元兴奋性的改变。前额叶皮质（PFC）是另一个参与认知功能并表达胰岛素受体的脑区。在此，我们运用电生理、分子和免疫细胞化学技术，研究胰岛素对脑片突触外GABA受体介导的强直电流的影响。我们发现，胰岛素（20 - 500 nM）可增加GABA介导的强直电流。我们的结果表明，胰岛素可促进突触外GABA受体从细胞质向细胞膜的转运。蛋白质印迹分析和免疫细胞化学显示，PFC突触外GABA受体含有α-5和δ亚基。胰岛素对强直电流的作用降低了PFC 5 - 6层细胞的放电频率和神经元兴奋性。胰岛素的这些作用依赖于PI3K酶的激活，PI3K酶是脑内胰岛素反应的关键介质。综上所述，这些结果表明，胰岛素对GABA介导的强直电流的调节可改变PFC内神经回路的活动。这些作用有助于解释与胰岛素信号变化相关的认知过程改变。
