神经元结构和突触可塑性是学习与记忆的主要机制之一，树突动态变化、突触传递和新生蛋白增加是其产生的主要原因。但是，中枢神经环路构建、功能和可塑性的表观遗传调控机制还缺少详尽的研究。本项目拟联合运用生物正交非天然氨基酸标记（BONCAT）和蛋白质谱测序技术筛选视觉条件刺激诱导的新生蛋白组分；运用在体神经元三维重构和电生理记录等技术，研究神经环路构建和和可塑性产生的内在机制；通过研究HDAC和β-catenin的相互作用及信号途径，阐释I类组蛋白去乙酰化酶（HDAC1/2/3/8）所扮演的不同角色，探索表观遗传修饰对神经环路结构功能的调控以及对视觉逃避行为的影响和拯救作用。通过本项目的研究，旨在筛选参与视觉条件刺激调控的新生蛋白组份，阐明中枢神经环路构建、功能和可塑性的表观遗传调控机制，建立视觉条件刺激研究中枢神经环路可塑性的动物模型。

Neural structural and synaptic plasticity are thought to be one of the major neural mechanism for learning and memory. Many studies have shown that neural circuit integrates visually-guided information and mediates experience-dependent synaptic and behavioral plasticity. Dynamic changes in dendritic structure, synaptic transmission and newly-synthesized proteins underlie the synaptic and structural plasticity in vitro and intact animals. Histone deacetylase (HDAC) affects neural development and mediates neurological diseases by regulating transcription factor as a co-factor. However, little is known the epigenetic regulation of structural, functional and plasticity in vivo. This project is intended to combine the use of bio-orthogonal noncanonical amino acid tagging (BONCAT) and protein mass spectrometry sequencing to screen for newly-synthesized proteins in response to visual conditioning stimuli. We will use the multi-disciplined methods of three-dimensional reconstruction and electrophysiological recording in vivo to study the effect of visual conditioning on the neural circuit and plasticity in the central nervous system. We propose to investigate the distinct roles of class I histone deacetylases of HDAC1/2/3/8, which would demonstrate the effect of epigenetic modification on the neural circuit function and visual avoidance behavior by elucidation of the relationship between HDAC and β-catenin. The aim of the project is to screen the newly-synthesized proteins involved in visual conditioning based neural circuit plasticity and elucidate the epigenetic regulation of neural circuit formation, function and plasticity of the central neural circuit. We expect that the ongoing proposal would potentially provide a powerful Xenopus model for the study of the neural circuit plasticity and function in vivo.