小儿接受全麻对神经系统发育的影响逐渐受到关注，然而具体机制不清。γ-氨基丁酸（GABA）是中枢神经系统重要的抑制性神经递质，也是全麻药物作用的一个重要靶点，其异常与多种精神类疾病的发生密切相关。我们前期研究提示全麻药物通过调控组蛋白去乙酰化酶影响GABA能神经元的发育而造成神经功能异常。为阐明该问题，本项目拟以GAD67-GFP转基因小鼠为研究工具，以目前临床上最常用的吸入性全麻药物七氟醚为研究对象，首先采用神经形态学及分子生物学方法，明确七氟醚对GABA能神经元发育的作用，进而围绕组蛋白去乙酰化酶可能参与的表观遗传学调控分析七氟醚影响GABA能神经元发育的分子机制。该问题的深入剖析对于进一步阐明全麻的毒性机理具有重要的理论意义，并对于临床小儿麻醉的方案的完善具有极重要的现实意义

The influence of general anaesthesia on neurodevelopment is attracting more and more attentions. Mounting evidence suggests that exposure to general anaesthetics may induce neurological sequelae, while the underlying mechanisms are unclear. γ-aminobutyric acid (GABA) is the most important inhibitory neurotransmitters in the central nervous system, and is also one of the most important targets of general anaesthesia. Disorder of GABAergic neurons is related with many mental diseases and neurodeficits. Based on previous studies and our preliminary data, we proposed that general anesthetics might cause mental disorders through influencing development of GABAergic transmission. To address this question, based on the GAD67-GFP transgenic mice, we first explore the influence of the commonly-used inhaled anaesthetic sevoflurane. We then sought to clarify the effects of anaesthetics on development of GABAergic neurons with methods including morphology, neurophysiology and molecular biology. The epigenetic modulation induced by histone deacetylases underlying general anaesthesia on development of GABAergic neurons will also be studied. Our study will be helpful for further clarifying the mechanisms of neonatal general anaesthesia on brain dysfunction. More importantly, our study may provide important suggestions on rational decision on proper strategies of pediatric general anaesthesia.