Assessment of neural activity in the specific brain area is critical for understanding the circuit mechanisms underlying altered brain function and behaviors. A number of immediate early genes (IEGs) that are rapidly transcribed in neuronal cells in response to synaptic activity have been used as markers for neuronal activity. However, protein detection of IEGs requires translation, and the amount of newly synthesized gene product is usually insufficient to detect using western blotting, limiting their utility in western blot analysis of brain tissues for comparison of basal activity between control and genetically modified animals. Here, we show that the phosphorylation status of eukaryotic elongation factor-2 (eEF2) rapidly changes in response to synaptic and neural activities. Intraperitoneal injections of the GABA A receptor (GABAAR) antagonist picrotoxin and the glycine receptor antagonist brucine rapidly dephosphorylated eEF2. Conversely, potentiation of GABAARs or inhibition of AMPA receptors (AMPARs) induced rapid phosphorylation of eEF2 in both the hippocampus and forebrain of mice. Chemogenetic suppression of hippocampal principal neuron activity promoted eEF2 phosphorylation. Novel context exploration and acute restraint stress rapidly modified the phosphorylation status of hippocampal eEF2. Furthermore, the hippocampal eEF2 phosphorylation levels under basal conditions were reduced in mice exhibiting epilepsy and abnormally enhanced excitability in CA3 pyramidal neurons. Collectively, the results indicated that eEF2 phosphorylation status is sensitive to neural activity and the ratio of phosphorylated eEF2 to total eEF2 could be a molecular signature for estimating neural activity in a specific brain area.

中文翻译：

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真核延伸因子 2 的磷酸化状态表明大脑中的神经活动

评估特定大脑区域的神经活动对于了解改变大脑功能和行为的电路机制至关重要。许多在神经元细胞中响应突触活动而迅速转录的即刻早期基因 (IEG) 已被用作神经元活动的标志物。然而，IEG 的蛋白质检测需要翻译，并且新合成的基因产物的数量通常不足以使用蛋白质印迹进行检测，这限制了它们在脑组织蛋白质印迹分析中用于比较对照和转基因动物之间的基础活性的实用性。在这里，我们表明真核延伸因子 2 (eEF2) 的磷酸化状态会随着突触和神经活动而迅速变化。腹膜内注射 GABA A 受体 (GABAAR) 拮抗剂印防己毒素和甘氨酸受体拮抗剂马钱子碱可迅速使 eEF2 去磷酸化。相反，GABAARs 的增强或 AMPA 受体 (AMPARs) 的抑制会诱导小鼠海马和前脑中 eEF2 的快速磷酸化。海马主要神经元活动的化学遗传学抑制促进了 eEF2 磷酸化。新的环境探索和急性约束压力迅速改变了海马 eEF2 的磷酸化状态。此外，在表现出癫痫的小鼠中，基础条件下的海马 eEF2 磷酸化水平降低，并且 CA3 锥体神经元的兴奋性异常增强。集体，