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

GABA能中间神经元的突触连接介导皮质柱中的局部、前馈或反馈抑制

• 批准号: 111824096
• 负责人: Professor Dr. Jochen Ferdinand Staiger
• 金额: --
• 依托单位: Institut für Neuroanatomie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/111824096?language=en
• 关键词: Synaptic; connections; GABAergic; interneurons; mediating

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.

GABA 能中间神经元的巨大多样性表明，个体类型首先形成一个连续体，而不是一组定义的类别。这种令人惊叹的多样性使得最近就单个 GABA 能细胞类型的一组定义特征达成一致成为可能（Ascoli 等，2008）。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已得到改进，使其能够成功进行分析：（i）转基因动物，用 GFP 对 GABA 能中间神经元亚群进行特定标记，从而可以事先识别这些最罕见的细胞类型； (ii) 结合配对记录和通过谷氨酸释放进行映射连接。在这里，我们建议通过以下体外方法研究皮质微电路，其中 GABA 能中间神经元被整合到其中： (ii)通过多重单细胞逆转录PCR对所有细胞进行分子鉴定； (iii) 探究不同类型中间神经元丘脑输入的层特异性分布； （iv）通过释放谷氨酸将这些细胞的输入映射到层和列特异性马尔默中，以及（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质中的抑制回路进行精确分析（见下文）。这些数据将使我们能够更好地了解 GABA 能中间神经元如何促进皮层柱内和皮层柱之间的触觉信息的处理。