Department of Physiology and Neurobiology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel.
Brain Res. 2012 Sep 7;1472:99-106. doi: 10.1016/j.brainres.2012.05.057. Epub 2012 Jul 14.
Psychological stress may lead to long-lasting brain dysfunction, specifically altered emotional and cognitive capabilities. Previous studies have demonstrated persistent changes in the expression of key cholinergic genes in the neocortex and hippocampus following stress with muscarinic receptor-mediated enhanced excitability. In the present study we examined cholinergic-mediated glutamatergic transmission in the hippocampus of mice after exposure to stress and its potential role in synaptic plasticity and altered behavior. Adult male mice were tested one month after repeated forced swimming test. Non-treated age-matched animals served as controls. Electrophysiological recordings were performed in the acute in-vitro slice preparation. CA1 pyramidal neurons were recorded using whole cell patch configuration. Extracellular recordings were done in response to Shaffer collaterals (SC) or stratum orien (SO) stimulation. Animal behavior in response to inhibition of acetylcholinesterase (AChE) was tested in open field paradigms. In whole cell patch recordings the frequency of excitatory post-synaptic currents (EPSCs) was significantly increased in response to muscarinic activation in stress-exposed animals. This enhanced cholinergic-modulated excitatory transmission is associated with facilitation of long-term potentiation (LTP) in response to tetanic stimulation at the SO but not at the SC. Stress-related behavioral modulation via central cholinergic pathways was enhanced by the central AChE inhibitor, physostigmine, thus further supporting the notion that stress is associated with long lasting hypersensitivity to acetylcholine. Our results revealed a pathway-specific enhancement of cholinergic-dependent glutamatergic transmission in the hippocampus after stress. These changes may underlie specific hippocampal malfunction, including cognitive and emotional disturbances, as observed in patients with post-traumatic stress disorder (PTSD).
心理压力可能导致长期的大脑功能障碍，特别是改变情绪和认知能力。以前的研究表明，在经历了与毒蕈碱受体介导的兴奋性增强相关的应激后，新皮层和海马体中的关键胆碱能基因表达持续发生变化。在本研究中，我们研究了应激后小鼠海马体内的胆碱能介导的谷氨酸能传递及其在突触可塑性和行为改变中的潜在作用。雄性成年小鼠在重复强迫游泳测试一个月后进行测试。未处理的同龄动物作为对照。在急性离体切片制备中进行电生理记录。使用全细胞膜片钳配置记录 CA1 锥体神经元。对 Schaffer 侧支 (SC) 或 stratum orien (SO) 刺激做出细胞外记录。通过在开阔场范式中测试对乙酰胆碱酯酶 (AChE) 的抑制来测试动物行为。在全细胞膜片钳记录中，在应激暴露的动物中，通过毒蕈碱激活，兴奋性突触后电流 (EPSC) 的频率显着增加。这种增强的胆碱能调节的兴奋性传递与 SO 而非 SC 处的强直刺激引起的长时程增强 (LTP) 的易化相关。通过中枢胆碱能途径的应激相关行为调节通过中枢 AChE 抑制剂physostigmine 得到增强，因此进一步支持应激与乙酰胆碱的长期超敏反应相关的观点。我们的研究结果显示，应激后海马体内的胆碱能依赖性谷氨酸能传递出现了特定途径的增强。这些变化可能是特定的海马体功能障碍的基础，包括创伤后应激障碍 (PTSD) 患者中观察到的认知和情绪障碍。
