Luo Fei, Guo Nan-Nan, Li Si-Hai, Tang Hua, Liu Ying, Zhang Yu
Center for Neuropsychiatric Diseases, Institute of Life Science, Nanchang University, Nanchang 330031, China.
Institute of Neurobiology & State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Neuropharmacology. 2014 Aug;83:89-98. doi: 10.1016/j.neuropharm.2014.03.020. Epub 2014 Apr 12.
The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of β1-adrenoceptor (β1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that β1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the β1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that β1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain β1-AR-induced PFC dysfunction.
前额叶皮质（PFC）在认知功能中起关键作用，包括工作记忆、注意力调节和行为抑制。已表明向PFC微量注射β1肾上腺素能受体（β1-AR）激动剂会损害PFC认知功能。然而，其潜在的细胞和分子机制尚未确定。在本研究中，我们测试了β1-AR介导的兴奋性突触传递调节导致PFC功能障碍这一假设。我们发现：1）β1-AR激动剂多巴酚丁胺（Dobu）抑制了诱发兴奋性突触后电流（eEPSCs）的幅度。2）Dobu显著抑制了微小兴奋性突触后电流（mEPSCs）的频率和幅度。3）Dobu抑制的谷氨酸释放是通过降低释放概率和可释放囊泡数量介导的。4）Dobu通过突触后PKA依赖途径抑制了谷氨酸或NMDA微量施加诱发的内向电流。本研究表明，β1-AR激活通过突触前和突触后PKA依赖机制抑制内侧前额叶皮质（mPFC）的兴奋性突触传递。我们的结果可能提供一种细胞和分子机制，有助于解释β1-AR诱导的PFC功能障碍。
