肾上腺素能β1受体介导前额叶皮层认知功能紊乱的机制研究

前额叶皮层在学习记忆、行为的计划和组织等脑的许多高级功能中起着关键作用。 应激导致去甲肾上腺素（NE）分泌增加，通过作用于前额叶皮层肾上腺素能β1受体（β1受体）损害认知功能。申请人工作揭示，前额叶皮层β1受体激活后通过PKA依赖性机制降低锥体细胞谷氨酸囊泡释放概率和数目（Luo et al., Neuropharmacology, 2014）。然而，β1受体对前额叶锥体细胞上GABA能突触传递的调控效应及机制尚不清楚。我们的预实验表明，β1受体在前额叶多类GABA能中间神经元均有分布, 且β1受体激活调控锥体细胞GABA能突触传递。阐明β1受体对前额叶锥体神经元上兴奋性和抑制性突触输入的调控，有助于理解应激损害认知功能的突触机制。本项目系统地研究β1受体激活对前额叶锥体细胞GABA能突触传递的调控，并分析其潜在的胞内和突触机理。本工作为帮助理解应激损害前额叶认知功能的机制提供理论依据。

The prefrontal cortex (PFC) is a cortical region crucial for learning and memory, behavioral planning and decision making. High levels of Noradrenaline (NE) release during stress impair PFC functions via β1 adrenoceptors (ARs). Recently, the applicant reports that β1-AR activation suppresses glutamatergic transmission through decreasing both the glutamate release probability and the number of releasable quanta via a PKA-dependent pathway (Luo et al., Neuropharmacology, 2014). However, it is unclear how β1-AR stimulation modulates GABAergic transmission in the PFC. Immunohistochemical result in our laboratory indicates that β1-ARs are expressed in a majority of GABAergic interneurons in the PFC, and β1-AR activation regulates GABAergic transmission in PFC layer 5/6 pyramidal neurons. Given that pyramidal neurons in the deep layers of the PFC integrate multiple glutamate and GABA inputs, and, through such networks, the PFC guides complex cognitive functions, in this current study, we seek to investigate the β1-AR regulation of GABAergic transmission in PFC and its potential cellular mechanism. The present work may help to comprehensively understand the cellular mechanism underlying cognitive dysfunction under stress exposure.