Curtailing Effect of Awakening on Visual Responses of Cortical Neurons by Cholinergic Activation of Inhibitory Circuits
Curtailing Effect of Awakening on Visual Responses of Cortical Neurons by Cholinergic Activation of Inhibitory Circuits
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DOI：
10.1523/jneurosci.0863-14.2014
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
R. Kimura;Mir-shahram Safari;J. Mirnajafi-zadeh;Rie Kimura;Teppei Ebina;Y. Yanagawa;K. Sohya;T. Tsumoto
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文献类型：
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作者：
R. Kimura;Mir-shahram Safari;J. Mirnajafi-zadeh;Rie Kimura;Teppei Ebina;Y. Yanagawa;K. Sohya;T. Tsumoto
大脑皮层神经元的视觉反应性随大脑状态而变化。这种变化背后的神经回路机制尚不清楚。通过应用在体双光子功能性钙成像的方法，在转基因大鼠中，GABA能神经元表达荧光蛋白，我们分析了视觉反应特性的变化，当动物从麻醉中醒来时，皮层神经元。在清醒状态下，GABA能神经元的视觉反应的幅度和可靠性增加，而兴奋性神经元的反应衰减变得更快。为了测试基底前脑（BF）胆碱能投射是否参与这些变化，我们分析了BF的电和光遗传学激活对小鼠皮层神经元视觉反应的影响，在体内成像和全细胞记录。电BF刺激麻醉动物引起相同方向的变化，在视觉反应的两组神经元觉醒。光遗传激活增加GABA能神经元视觉诱发动作电位的频率，但诱导延迟超极化，停止兴奋性神经元动作电位的晚期产生。切片制备的药理学分析表明，光活化诱导的第1层GABA能神经元的去极化被烟碱受体拮抗剂阻断，而非快速尖峰层2/3 GABA能神经元仅被烟碱和毒蕈碱受体拮抗剂阻断。这些结果表明，觉醒的效果主要是通过烟碱激活第1层GABA能神经元和混合烟碱/毒蕈碱激活第2/3层非快速发放GABA能神经元，这两者共同减少兴奋性神经元的视觉反应。
Visual responsiveness of cortical neurons changes depending on the brain state. Neural circuit mechanism underlying this change is unclear. By applying the method of in vivo two-photon functional calcium imaging to transgenic rats in which GABAergic neurons express fluorescent protein, we analyzed changes in visual response properties of cortical neurons when animals became awakened from anesthesia. In the awake state, the magnitude and reliability of visual responses of GABAergic neurons increased whereas the decay of responses of excitatory neurons became faster. To test whether the basal forebrain (BF) cholinergic projection is involved in these changes, we analyzed effects of electrical and optogenetic activation of BF on visual responses of mouse cortical neurons with in vivo imaging and whole-cell recordings. Electrical BF stimulation in anesthetized animals induced the same direction of changes in visual responses of both groups of neurons as awakening. Optogenetic activation increased the frequency of visually evoked action potentials in GABAergic neurons but induced the delayed hyperpolarization that ceased the late generation of action potentials in excitatory neurons. Pharmacological analysis in slice preparations revealed that photoactivation-induced depolarization of layer 1 GABAergic neurons was blocked by a nicotinic receptor antagonist, whereas non–fast-spiking layer 2/3 GABAergic neurons was blocked only by the application of both nicotinic and muscarinic receptor antagonists. These results suggest that the effect of awakening is mediated mainly through nicotinic activation of layer 1 GABAergic neurons and mixed nicotinic/muscarinic activation of layer 2/3 non–fast-spiking GABAergic neurons, which together curtails the visual responses of excitatory neurons.