C末端结合蛋白2（CtBP2）主要作为转录共抑制因子在多种器官调控基因表达。对神经系统内CtBP2的研究主要集中在它作为带状突触结构蛋白的特殊功能上。然而除了带状突触分布的少量区域，CtBP2在脑内广泛表达甚至可能参与神经退行性疾病发病，但目前对CtBP2在神经元内的生理功能了解极少。我们发现CtBP2在CA3神经元细胞核显著高表达。我们分别敲降背侧和腹侧海马CA3神经元CtBP2并进行了认知行为和生化分析，发现敲降背侧而非腹侧海马CA3 CtBP2特异性诱发空间记忆缺陷，且与AMPA受体亚基GluR2表达降低有关。在本项目中，我们将综合运用分子与细胞生物学、电生理、行为学等手段揭示背侧海马CA3神经元CtBP2调节空间记忆的作用和分子机制。研究成果将为CtBP2在神经元中的生理功能提供新的内容，为背侧海马CA3调控空间记忆提供机制解释，为相关神经疾病的治疗和诊断提供新的线索。

C-terminal binding proteins 2 (CtBP2) mainly functions as a transcriptional co-suppresser to regulator gene expression in multiple organs. In the nervous system, studies of CtBP2 have been focused on its special role as a structural protein in ribbon synapses. However, besides the limited areas where ribbon synapses are distributed, CtBP2 is widely expressed in the brain and may even participate in the pathogenic process of neurodegenerative diseases. However, our knowledge of CtBP2 physiological function in neurons is rather limited. Here we found that CtBP2 is significantly enriched in hippocampal CA3 neuronal nuclei. We knocked down CtBP2 expression in the dorsal and ventral hippocampus and performed cognitive behavioral and biochemical analysis. We found that CtBP2 knockdown in the dorsal but not in the ventral, hippocampal CA3 neurons specifically induced spatial memory deficits, which was associated with reduction of GluR2, an AMPA receptor subunit, expression. In this project, we aim to reveal the functional mechanisms of CtBP2 in the dorsal hippocampal CA3 neurons in the regulation of spatial memory through systematic application of molecular and cellular biology, electrophysiology, behavioral assays, and pharmacological techniques. The results will improve our knowledge of CtBP2 functions in mature neurons, provide explanation for spatial memory regulation by dorsal hippocampal CA3, and give new clues for the therapy and diagnosis of relevant neurological diseases.