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      Morphological and Functional Characterization of Non-fast-Spiking GABAergic Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex

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          Abstract

          GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons, 2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons, 4) intra-columnar projecting VIP-like interneurons, and 5) locally projecting neurogliaform-like interneurons. Trans-columnar projecting interneurons are one of the most striking interneuron types, which have not been described so far in Layer 4. They feature extensive axonal collateralization not only in their home barrel but also in adjacent barrels. Furthermore, we identified that most of the L4 nFS interneurons express somatostatin, while few are positive for the transcription factor Prox1. The morphological and electrophysiological characterization of different L4 nFS interneuron types presented here provides insights into their synaptic connectivity and functional role in cortical information processing.

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          Interneurons of the neocortical inhibitory system.

          Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80% of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.
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            Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex.

            Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.
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              Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons.

              An understanding of the diversity of cortical GABAergic interneurons is critical to understand the function of the cerebral cortex. Recent data suggest that neurons expressing three markers, the Ca2+-binding protein parvalbumin (PV), the neuropeptide somatostatin (SST), and the ionotropic serotonin receptor 5HT3a (5HT3aR) account for nearly 100% of neocortical interneurons. Interneurons expressing each of these markers have a different embryological origin. Each group includes several types of interneurons that differ in morphological and electrophysiological properties and likely have different functions in the cortical circuit. The PV group accounts for ∼40% of GABAergic neurons and includes fast spiking basket cells and chandelier cells. The SST group, which represents ∼30% of GABAergic neurons, includes the Martinotti cells and a set of neurons that specifically target layerIV. The 5HT3aR group, which also accounts for ∼30% of the total interneuronal population, is heterogeneous and includes all of the neurons that express the neuropeptide VIP, as well as an equally numerous subgroup of neurons that do not express VIP and includes neurogliaform cells. The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states and behavioral contexts. Copyright © 2010 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Cereb Cortex
                Cereb. Cortex
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                April 2018
                10 January 2018
                10 January 2018
                : 28
                : 4
                : 1439-1457
                Affiliations
                [1 ]Institute of Neuroscience and Medicine, INM-2 and INM-10, Research Centre Jülich, Jülich, Germany
                [2 ]Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany
                [3 ]School of Electronic Engineering, Nanjing Xiaozhuang University, Nanjing, P.R. China
                [4 ]Jülich Aachen Research Alliance, Translational Brain Medicine (JARA Brain), Aachen, Germany
                [5 ]Department of Biosystems Sciences and Engineering, Bio Engineering Lab, ETH Zürich, Basel, Switzerland
                Author notes
                Address correspondence to Dirk Feldmeyer, Institute of Neuroscience and Medicine (INM-2), Research Centre Jülich, D-52425 Jülich, Germany. Email: d.feldmeyer@ 123456fz-juelich.de

                Vishalini Emmenegger and Guanxiao Qi contributed equally to this work.

                Author information
                http://orcid.org/0000-0003-3195-7772
                Article
                bhx352
                10.1093/cercor/bhx352
                6093438
                29329401
                4bea3d45-7f71-4c2c-91d1-73c1bce54004
                © The Author(s) 2018. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 26 September 2017
                : 12 December 2017
                Page count
                Pages: 19
                Funding
                Funded by: Helmholtz Society, the DFG Research Group
                Funded by: DFG International Research Training Group
                Award ID: 1328
                Funded by: Natural Science Fund for Colleges
                Funded by: Universities in the Jiangsu
                Award ID: 14KJB140007
                Categories
                Original Articles

                Neurology
                barrel cortex,gabaergic interneuron,layer 4,non-fast spiking
                Neurology
                barrel cortex, gabaergic interneuron, layer 4, non-fast spiking

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