Aramakis V B, Bandrowski A E, Ashe J H
Department of Neuroscience, University of California, Riverside 92521, USA.
Brain Res. 1997 May 30;758(1-2):107-17. doi: 10.1016/s0006-8993(97)00205-9.
The present study is concerned with the ability of muscarinic actions of acetylcholine (ACh) to modulate glutamate and gamma-aminobutyric acid (GABA)-mediated synaptic transmission in the in vitro rat auditory cortex. Whole-cell patch clamp recordings were obtained from layer II-III pyramidal neurons, and the fast-EPSP (AMPA/kainate), fast-IPSP (GABA(A)), and slow-IPSP (GABA(B)), were elicited following a stimulus to deep gray/white matter. Acetyl-beta-methylcholine (MCh), a muscarinic receptor agonist, applied by either superfusion or iontophoresis, produced an atropine-sensitive increase or decrease in the amplitude of the fast-EPSP. The effect of MCh could be predicted by the response of the fast-EPSP to paired-pulse stimulation (i.e. a conditioning pulse followed 300 ms later by a test pulse). The fast-EPSP was decreased in amplitude by MCh in cases where the test-EPSP was suppressed in the pre-MCh condition, and increased in amplitude when the test-EPSP was facilitated. The fast- and slow-IPSPs were always reduced by MCh. In several experiments, the strength of synaptic inhibition was systematically modified by varying stimulus intensity. When the fast-EPSP was elicited in the absence of IPSPs, it was decreased in amplitude by MCh. However, when the fast-EPSP was elicited in conjunction with large IPSPs it was increased in amplitude during MCh. Because the magnitude of the fast-EPSP is influenced by the degree of temporal overlap with IPSPs, it was hypothesized that enhancement of the fast-EPSP was the result of disinhibition produced as a consequence of muscarinic reduction of GABAergic IPSPs. This view was supported by the finding that MCh could reduce the amplitude of pharmacologically isolated GABAergic IPSPs (i.e. elicited in the absence of glutamatergic transmission). Our results suggest that ACh at muscarinic receptors can modify fast glutamatergic neurotransmission differently as a function of strength of inhibition, to suppress that produced by 'weak' inputs and enhance that produced by 'strong' inputs.
本研究关注乙酰胆碱（ACh）的毒蕈碱样作用调节体外培养的大鼠听觉皮层中谷氨酸和γ-氨基丁酸（GABA）介导的突触传递的能力。采用全细胞膜片钳记录技术，从II-III层锥体神经元获取记录，刺激深部灰质/白质后诱发快速兴奋性突触后电位（fast-EPSP，AMPA/海人藻酸受体介导）、快速抑制性突触后电位（fast-IPSP，GABA(A)受体介导）和慢速抑制性突触后电位（slow-IPSP，GABA(B)受体介导）。通过灌流或离子导入施加毒蕈碱受体激动剂乙酰-β-甲基胆碱（MCh），可使快速兴奋性突触后电位的幅度产生阿托品敏感的增加或降低。MCh的作用可通过快速兴奋性突触后电位对配对脉冲刺激（即一个条件脉冲后300毫秒施加一个测试脉冲）的反应来预测。在MCh施加前测试兴奋性突触后电位被抑制的情况下，MCh可使快速兴奋性突触后电位的幅度降低；而当测试兴奋性突触后电位被易化时，其幅度增加。快速和慢速抑制性突触后电位总是被MCh降低。在一些实验中，通过改变刺激强度系统地改变突触抑制的强度。当在没有抑制性突触后电位的情况下诱发快速兴奋性突触后电位时，MCh可使其幅度降低。然而，当快速兴奋性突触后电位与大的抑制性突触后电位同时诱发时，在MCh作用期间其幅度增加。由于快速兴奋性突触后电位的幅度受与抑制性突触后电位时间重叠程度的影响，因此推测快速兴奋性突触后电位的增强是毒蕈碱样作用降低GABA能抑制性突触后电位导致去抑制的结果。这一观点得到以下发现的支持：MCh可降低药理学分离的GABA能抑制性突触后电位的幅度（即在没有谷氨酸能传递的情况下诱发）。我们的结果表明，毒蕈碱受体处的ACh可根据抑制强度不同地调节快速谷氨酸能神经传递，抑制“弱”输入产生的神经传递，增强“强”输入产生的神经传递。
