Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
J Neurophysiol. 2012 Jun;107(11):3116-34. doi: 10.1152/jn.00917.2011. Epub 2012 Mar 7.
Synaptic interactions between nearby excitatory and inhibitory neurons in the neocortex are thought to play fundamental roles in sensory processing. Here, we have combined optogenetic stimulation, whole cell recordings, and computational modeling to define key functional microcircuits within layer 2/3 of mouse primary somatosensory barrel cortex. In vitro optogenetic stimulation of excitatory layer 2/3 neurons expressing channelrhodopsin-2 evoked a rapid sequence of excitation followed by inhibition. Fast-spiking (FS) GABAergic neurons received large-amplitude, fast-rising depolarizing postsynaptic potentials, often driving action potentials. In contrast, the same optogenetic stimulus evoked small-amplitude, subthreshold postsynaptic potentials in excitatory and non-fast-spiking (NFS) GABAergic neurons. To understand the synaptic mechanisms underlying this network activity, we investigated unitary synaptic connectivity through multiple simultaneous whole cell recordings. FS GABAergic neurons received unitary excitatory postsynaptic potentials with higher probability, larger amplitudes, and faster kinetics compared with NFS GABAergic neurons and other excitatory neurons. Both FS and NFS GABAergic neurons evoked robust inhibition on postsynaptic layer 2/3 neurons. A simple computational model based on the experimentally determined electrophysiological properties of the different classes of layer 2/3 neurons and their unitary synaptic connectivity accounted for key aspects of the network activity evoked by optogenetic stimulation, including the strong recruitment of FS GABAergic neurons acting to suppress firing of excitatory neurons. We conclude that FS GABAergic neurons play an important role in neocortical microcircuit function through their strong local synaptic connectivity, which might contribute to driving sparse coding in excitatory layer 2/3 neurons of mouse barrel cortex in vivo.
在新皮层中，邻近的兴奋性和抑制性神经元之间的突触相互作用被认为在感觉处理中发挥着基本作用。在这里，我们结合光遗传学刺激、全细胞膜片钳记录和计算建模来定义小鼠初级体感皮层 2/3 层中的关键功能微电路。在体外表达通道视紫红质-2 的兴奋性 2/3 层神经元的光遗传学刺激引发了快速的兴奋 followed 抑制序列。快速放电（FS）GABA 能神经元接收大振幅、快速上升的去极化突触后电位，通常驱动动作电位。相比之下，相同的光遗传学刺激在兴奋性和非快速放电（NFS）GABA 能神经元中诱发小幅度、阈下突触后电位。为了理解这种网络活动的突触机制，我们通过多个同时的全细胞膜片钳记录研究了单元突触连接。FS GABA 能神经元接收到的单元兴奋性突触后电位具有更高的概率、更大的振幅和更快的动力学，与 NFS GABA 能神经元和其他兴奋性神经元相比。FS 和 NFS GABA 能神经元均可在突触后 2/3 层神经元上诱发强烈的抑制。一个基于不同类型的 2/3 层神经元的实验确定的电生理特性和它们的单元突触连接的简单计算模型解释了光遗传学刺激诱发的网络活动的关键方面，包括 FS GABA 能神经元的强烈募集，其作用是抑制兴奋性神经元的放电。我们得出结论，FS GABA 能神经元通过其强大的局部突触连接在新皮层微电路功能中发挥重要作用，这可能有助于驱动体内小鼠桶皮层 2/3 层兴奋性神经元的稀疏编码。
