缺勤性癫痫是皮质-丘脑皮质(CTC)网络内的过度兴奋,然而,细胞和分子水平的潜在致病机制仍在阐明,并且似乎是多因素的。功能失调的前馈抑制(FFI)被认为是失神癫痫发作的一个原因。以前,我们报道了在失神癫痫stargazer小鼠模型的CTC网络中,小白蛋白阳性(PV+)中间神经元的兴奋改变.此外,在该模型中还发现了GABA能神经传递的下游变化.我们目前的研究评估了功能失调的FFI是否会影响观星者初级体感皮层(SoCx)中GABAA受体(GABAAR)亚基的表达。使用Westernblotting(WB)评估GABAAR亚基α1,α3,α4,α5,β2,β3,γ2和δ的整体组织表达,而生化分离的亚细胞部分评估了α和δ亚基。我们发现GABAARα1的组织和突触表达显着降低,分别为18%和12.2%,分别。然而,免疫金-细胞化学电子显微镜(ICC-EM),专门在PV中间神经元及其靶标之间的突触处评估GABAARα1,无显著性差异。这些数据表明阶段性GABAARα1的丧失,表明GABA能抑制改变,再加上功能失调的FFI,可能是导致失神癫痫发作产生或维持的一种机制。
Absence seizures are hyperexcitations within the cortico-thalamocortical (CTC) network, however the underlying causative mechanisms at the cellular and molecular level are still being elucidated and appear to be multifactorial. Dysfunctional feed-forward inhibition (FFI) is implicated as one cause of absence seizures. Previously, we reported altered excitation onto parvalbumin-positive (PV+) interneurons in the CTC network of the stargazer mouse model of absence epilepsy. In addition, downstream changes in GABAergic neurotransmission have also been identified in this model. Our current study assessed whether dysfunctional FFI affects GABAA receptor (GABAAR) subunit expression in the stargazer primary somatosensory cortex (SoCx). Global tissue expression of GABAAR subunits α1, α3, α4, α5, β2, β3, γ2 and δ were assessed using Western blotting (WB), while biochemically isolated subcellular fractions were assessed for the α and δ subunits. We found significant reductions in tissue and synaptic expression of GABAAR α1, 18% and 12.2%, respectively. However, immunogold-cytochemistry electron microscopy (ICC-EM), conducted to assess GABAAR α1 specifically at synapses between PV+ interneurons and their targets, showed no significant difference. These data demonstrate a loss of phasic GABAAR α1, indicating altered GABAergic inhibition which, coupled with dysfunctional FFI, could be one mechanism contributing to the generation or maintenance of absence seizures.