神经发育障碍疾病的显著特征是情感记忆异常。突触粘附蛋白MDGA1是该类疾病的易感基因。既往研究发现MDGA1可调控神经元兴奋抑制性平衡，且在大脑海马和缰核等情感记忆中枢选择性富集。然而，MDGA1调控情感记忆的作用和机制仍然未知。我们将采用免疫荧光、扩展显微、免疫印迹、膜片钳、转基因和行为学检测等技术进行研究。首先探明海马和缰核中MDGA1蛋白的细胞和突触分布；然后研究MDGA1敲除后海马和缰核中突触数量和功能，及突触功能基因表达、神经环路兴奋性以及情感记忆行为表征变化；最后将利用病毒注射结合转基因鼠特异性后天敲除及恢复海马或缰核中MDGA1表达后，再检测突触、神经环路兴奋性以及情感记忆行为表征变化，从而建立MDGA1神经环路特异性调控情感记忆行为的因果关系。通过上述研究，期望能为MDGA1功能异常造成的神经发育障碍疾病提供神经环路和分子机制，为情感记忆行为异常的防治提供新的分子靶点。

Neurodevelopmental diseases are featured by the comorbidities of memory and mood disorders. The synaptic adhesion protein - MDGA1 confers risks to such diseases. Previous studies have demonstrated that MDGA1 regulates the neuronal excitation/inhibition (E/I) balance and selectively expressed in the hippocampus and habenula, which are the major brain circuits to govern memory and mood. In this study, we propose to investigate the role of MDGA1 in regulation of memory and mood and its underlying mechanisms. We will employ the following techniques, including immunostaining, expansion microscopy, patch clamp, transgenic mouse and behavioral test. First, we will explicitly investigate the cell type and synaptic distribution of MDGA1 in the hippocampus and habenula. Then, we will count excitatory/inhibitory synaptic number, electrophysiologically examine synaptic function and investigate the gene expression that is essential for synaptic function in the hippocampus and habenula, and screen behavioral dysfunctions in MDGA1 knockout mice. Finally, we will combine the viral expression and transgenic strategy to selectively knockout or rescue MDGA1 in the hippocampus and habenula. We will investigate the changes in synapses, circuit excitability and memory/mood-related behavioral outcomes. In this way, we try to establish the casual relationship between the hippocampal and habenula MDGA1 expression and memory/mood-related behavioral phenotypes. Our study is meant to dissect the brain circuit and molecular mechanisms of MDGA1 dysfunction-linked behavioral disorders. While, the study may also provide a brain-circuit specific molecular target to treat brain disorders by tuning E/I balance.