14‐3‐3 proteins are a family of regulatory proteins that are abundantly expressed in the brain and enriched at the synapse. Dysfunctions of these proteins have been linked to neurodevelopmental and neuropsychiatric disorders. Our group has previously shown that functional inhibition of these proteins by a peptide inhibitor, difopein, in the mouse brain causes behavioural alterations and synaptic plasticity impairment in the hippocampus. Recently, we found an increased cFOS expression in difopein‐expressing dorsal CA1 pyramidal neurons, indicating enhanced neuronal activity by 14‐3‐3 inhibition in these cells. In this study, we used slice electrophysiology to determine the effects of 14‐3‐3 inhibition on the intrinsic excitability of CA1 pyramidal neurons from a transgenic 14‐3‐3 functional knockout (FKO) mouse line. Our data demonstrate an increase in intrinsic excitability associated with 14‐3‐3 inhibition, as well as reveal action potential firing pattern shifts after novelty‐induced hyperlocomotion in the 14‐3‐3 FKO mice. These results provide novel information on the role 14‐3‐3 proteins play in regulating intrinsic and activity‐dependent neuronal excitability in the hippocampus.

中文翻译：

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抑制 14-3-3 蛋白增加小鼠海马 CA1 锥体神经元的内在兴奋性

14-3-3 蛋白是一个调节蛋白家族，在大脑中大量表达并在突触处富集。这些蛋白质的功能障碍与神经发育和神经精神疾病有关。我们的研究小组之前已经证明，在小鼠大脑中，肽抑制剂二福平对这些蛋白质的功能抑制会导致海马体的行为改变和突触可塑性受损。最近，我们发现表达二福平的背侧 CA1 锥体神经元中 cFOS 表达增加，表明这些细胞中的 14-3-3 抑制增强了神经元活性。在本研究中，我们使用切片电生理学来确定 14-3-3 抑制对转基因 14-3-3 功能性敲除 (FKO) 小鼠系 CA1 锥体神经元内在兴奋性的影响。我们的数据证明了与 14-3-3 抑制相关的内在兴奋性增加，并揭示了 14-3-3 FKO 小鼠在新奇事物诱导的过度运动后动作电位放电模式的变化。这些结果提供了关于 14-3-3 蛋白在调节海马内在和活动依赖性神经元兴奋性中所发挥的作用的新信息。