丘脑-皮质输入对吊灯细胞和篮细胞的不同招募动态

Distinct recruitment dynamics of chandelier cells and basket cells by thalamocortical inputs

在皮质环路中存在的多种类型的GABA能中间神经元在抑制性控制中发挥着重要作用。其中吊灯细胞(轴突-轴突细胞)具有独特的形态特征,特异地支配锥体神经元的轴突起始段,被认为能抑制锥体神经元动作电位的产生及传导,从而对其输出起到终末抑制作用。同为快速放电的抑制性篮细胞在放电模式、分子组成和神经元抑制方面具有类似特征。然而和篮细胞不同的是,吊灯细胞的突触招募模式还鲜为人知。我们采用小鼠遗传学、光遗传学和离体膜片钳电生理等方法,研究了丘脑-皮质输入对内侧前额叶皮质中吊灯细胞和篮细胞的短时可塑性的作用。结果显示:丘脑-皮质输入使吊灯细胞产生起始小但短时程易化的突触反应,从而驱动吊灯细胞持续放电;与此相反,丘脑-皮质输入诱导篮细胞产生起始强但短时程抑制的突触反应,篮细胞只在输入起始时放电。总的来说,不同的突触招募动态模式进一步显示了吊灯细胞和篮细胞之间的差异,提示这两类快速放电中间神经元在皮质环路调控和生理功能中可能发挥不同的作用。

Diverse types of GABAergic interneurons tend to specialize in their inhibitory control of various aspects of cortical circuit operations.Among the most distinctive interneuron types,chandelier cells(i.e.,axo-axonic cells)are a bona fide cell type that specifically innervates pyramidal cells at the axon initial segment,the site of action potential initiation.Chandelier cells have been speculated to exert ultimate inhibitory control over pyramidal cell spiking.Thus,chandelier cells appear to share multiple similarities with basket cells,not only in firing pattern(fast spiking)and molecular components,but also in potentially perisomatic inhibitory control.Unlike basket cells,however,synaptic recruitment of chandelier cells is little known yet.Here,we examined the mediodorsal thalamocortical input to both chandelier cells and basket cells in medial prefrontal cortex,through combining mouse genetic,optogenetic and electrophysiological approaches.We demonstrated that this thalamocortical input produced initially weak,but facilitated synaptic responses at chandelier cells,which enabled chandelier cells to spike persistently.In contrast,this thalamocortical input evoked initially strong,but rapidly depressed synaptic responses at basket cells,and basket cells only fired at the initiation of input.Overall,the distinct synaptic recruitment dynamics further underscores the differences between chandelier cells and basket cells,suggesting that these two types of fast spiking interneurons play different roles in cortical circuit processing and physiological operation.