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，首先，个别类型形成了一个连续体，而不是一组定义的类别。就在最近，这种令人惊叹的变化使人们有可能就单个GABA能细胞类型的一组定义特征达成一致(Ascoli等人，2008年)。因此，来自不同群体的数据最终可能变得具有可比性。此外，研究皮质细胞连接性的技术现在已经改进到一定程度，这将使它们的成功分析成为可能：(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，使这些大多数稀有细胞类型的预先鉴定成为可能；(Ii)结合成对记录和通过谷氨酸去除来绘制连接性图。在此，我们建议通过以下体外方法研究GABA能中间神经元整合到其中的皮质微电路：(I)使用小白蛋白(PV)和血管五肽(VIP)转基因小鼠，允许明确地预先识别感兴趣的细胞；(Ii)通过多重单细胞逆转录聚合酶链式反应对所有细胞进行分子鉴定；(Iii)探索丘脑输入信号在不同类型中间神经元上的层特异性分布；(Iv)通过去掉谷氨酸，将这些细胞的输入映射到层特异性Marmer和柱特异性Marmer中；以及(V)对染色的神经元进行三维和定量重建，包括对其靶结构进行电子显微镜验证。这将导致在局部、前馈和反馈处理原则(见下文)的指导下，对新大脑皮层中的抑制电路进行精确分析。这些数据将使我们能够更好地理解GABA能中间神经元如何在皮质柱内和皮质柱之间对触觉信息的处理做出贡献。

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.