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

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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.