Synaptic connections of GABAergic interneurons mediating local, feedforward or feedback inhibition in a cortical column

gaba能中间神经元的巨大多样性表明，一开始个体类型形成了一个连续体，而不是一个定义的类别集合。这种惊人的多样性使得最近我们就个体gaba能细胞类型的一系列定义特征达成一致（Ascoli et al., 2008）。因此，来自不同群体的数据可能最终具有可比性。此外，研究皮质细胞连通性的技术现在已经得到了一定程度的改进，这将使它们能够成功地进行分析：(i)用GFP对gaba能中间神经元亚群进行特定标记的转基因动物，使这些大多数罕见的细胞类型的预先鉴定成为可能；（ii）结合成对记录和谷氨酸释放的映射连接。在这里，我们建议通过以下体外方法研究gaba能中间神经元整合的皮质微回路：(i)使用小白蛋白（PV）和血管肽肠肽（VIP）转基因小鼠，允许对感兴趣的细胞进行明确的预鉴定；（ii）通过多重单细胞逆转录PCR对所有细胞进行分子特异性鉴定；（iii）探索丘脑输入在不同类型中间神经元上的层特异性分布；（iv）通过释放谷氨酸来绘制这些细胞在层和柱特异性marmer中的输入图；(v)三维和定量地重建染色的神经元，包括对其目标结构的电子显微镜验证。这将导致在局部、前馈和反馈处理原则的指导下，对新皮层中的抑制回路进行精确分析（见下文）。这些数据将使我们更好地理解gaba能中间神经元是如何参与皮层柱内和跨皮层柱的触觉信息处理的。

The large diversity of GABAergic interneurons suggests for a start individual types forming a continuum rather than a defined set of classes. This stunning variety has made it possible just recently lo agree on a set of defining features for individual GABAergic cell types (Ascoli et al., 2008). Thus, data from different groups may fmally become comparable. In addifion, the techniques for studying the connectivity of cortical cells have now been refined to an extent that will enable their successful analysis: (i) transgenic animals with specific tagging of subpopulations of GABAergic interneurons with GFP making the prior identificafion of these mostly rare cell types possible; (ii) combinafion of paired recordings and mapping connectivity by glutamate uncaging.Here we suggest to study cortical microcircuits into which GABAergic interneurons are integrated by the following in vitro approach: (i) use parvalbumin (PV) and vasoacfive intestinal peptide (VIP) transgenic mice that allow an imambiguous pre-identification of cellsof- interest; (ii) molecularly specify all cells by multiplex single cell reverse transcripfion PCR; (iii) probe the layer-specific distribution of thalamic inputs onto the different types of interneurons; (iv) map the inputs of these cells in a layer- and column-specific marmer by uncaging glutamate and (v) reconstruct the stained neurons three-dimensionally and quantitatively, including an electron microscopic verification of their target structures. This will lead to a precise analysis of inhibitory circuits in the neocortex guided by the principles of local, feedforward and feedback processing (see below). These data will enable us to better understand how GABAergic interneurons contribute to the processing of tactile information within and across cortical columns.