In Vivo Optogenetic Stimulation of Neocortical Excitatory Neurons Drives Brain-State-Dependent Inhibition
In Vivo Optogenetic Stimulation of Neocortical Excitatory Neurons Drives Brain-State-Dependent Inhibition
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DOI：
10.1016/j.cub.2011.08.028
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发表时间：
2011-10-11
期刊：
影响因子：
9.2
通讯作者：
Petersen, Carl C. H.
中科院分区：
文献类型：
--
作者：
Mateo, Celine;Avermann, Michael;Petersen, Carl C. H.
背景：兴奋性和抑制性新皮层神经元之间的突触相互作用对哺乳动物的感觉知觉很重要。新皮层微回路中已鉴定神经元间的突触传递主要在体外脑切片制备中进行研究。在这里，我们通过双光子显微镜结合光遗传刺激的特异性和突触后兴奋性谷氨酸能神经元和gfp标记的抑制性gaba能神经元的全细胞记录的准确性，研究了体内脑状态依赖性的新皮层突触相互作用。结果：与位于同一皮层微回路内的非快速尖峰（NFS） gabaergy神经元和突触后兴奋性锥体神经元相比，通道视紫红质-2 （ChR2）刺激兴奋性第213层桶状皮质神经元引起的快速尖峰（FS） gabaergy神经元的去极化突触后电位和突触驱动动作电位更大、更快。在chr2表达神经元中引起的动作电位的数量表现出较低的试验间变异性，但突触后反应的变化强烈，并且近似线性地依赖于刺激前膜电位的自发驱动变化。兴奋性神经元的突触后反应具有反转电位，相对于动作电位阈值具有超极化，因此具有抑制性。突触后gaba能神经元的逆转电位接近动作电位阈值。突触后抑制性神经元优先从自发去极化的网络状态发射突触驱动的动作电位，NFS gabaergy神经元的状态依赖性调节强于FS gabaergy神经元。结论：抑制性神经元似乎主导了新皮层微回路功能，与兴奋性神经元相比，抑制性神经元接受更强的局部兴奋性突触输入并发射更多的动作电位。在小鼠2/3层桶状皮质中，我们提出抑制神经元的强状态依赖性募集驱动了执行稀疏编码的兴奋神经元之间的竞争。
Background: Synaptic interactions between excitatory and inhibitory neocortical neurons are important for mammalian sensory perception. Synaptic transmission between identified neurons within neocortical microcircuits has mainly been studied in brain slice preparations in vitro. Here, we investigate brain-state-dependent neocortical synaptic interactions in vivo by combining the specificity of optogenetic stimulation with the precision of whole-cell recordings from postsynaptic excitatory glutamatergic neurons and GFP-labeled inhibitory GABAergic neurons targeted through two-photon microscopy.Results: Channelrhodopsin-2 (ChR2) stimulation of excitatory layer 213 barrel cortex neurons evoked larger and faster depolarizing postsynaptic potentials and more synaptically driven action potentials in fast-spiking (FS) GABAergic neurons compared to both non-fast-spiking (NFS) GABAergic neurons and postsynaptic excitatory pyramidal neurons located within the same neocortical microcircuit. The number of action potentials evoked in ChR2-expressing neurons showed low trial-to-trial variability, but postsynaptic responses varied strongly with near-linear dependence upon spontaneously driven changes in prestimulus membrane potential. Postsynaptic responses in excitatory neurons had reversal potentials, which were hyperpolarized relative to action potential threshold and were therefore inhibitory. Reversal potentials measured in postsynaptic GABAergic neurons were close to action potential threshold. Postsynaptic inhibitory neurons preferentially fired synaptically driven action potentials from spontaneously depolarized network states, with stronger state-dependent modulation in NFS GABAergic neurons compared to FS GABAergic neurons.Conclusions: Inhibitory neurons appear to dominate neocortical microcircuit function, receiving stronger local excitatory synaptic input and firing more action potentials compared to excitatory neurons. In mouse layer 2/3 barrel cortex, we propose that strong state-dependent recruitment of inhibitory neurons drives competition among excitatory neurons enforcing sparse coding.