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      Inhibition of Inhibition in Visual Cortex: The Logic of Connections Between Molecularly Distinct Interneurons

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          Abstract

          Cortical inhibitory neurons contact each other to form a network of inhibitory synaptic connections. Our knowledge of the connectivity pattern underlying this inhibitory network is, however, still incomplete. Here we discover a simple and complementary interaction scheme between three large molecularly distinct interneuron populations in mouse visual cortex: Parvalbumin expressing interneurons strongly inhibit one another but, surprisingly, provide little inhibition to other populations. In contrast, somatostatin expressing interneurons avoid inhibiting one another, yet strongly inhibit all other populations. Finally, vasoactive intestinal peptide expressing interneurons preferentially inhibit somatostatin interneurons. This scheme occurs in supra- and infra-granular layers, suggesting that inhibitory networks operate similarly at the input and output of visual cortex. Thus, as the specificity of connections between excitatory neurons forms the basis for the cortical canonical circuit, the scheme described here outlines a standard connectivity pattern among cortical inhibitory neurons.

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          Most cited references44

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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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            A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex.

            A key obstacle to understanding neural circuits in the cerebral cortex is that of unraveling the diversity of GABAergic interneurons. This diversity poses general questions for neural circuit analysis: how are these interneuron cell types generated and assembled into stereotyped local circuits and how do they differentially contribute to circuit operations that underlie cortical functions ranging from perception to cognition? Using genetic engineering in mice, we have generated and characterized approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons. More select populations are captured by intersection of Cre and Flp drivers. Genetic targeting allows reliable identification, monitoring, and manipulation of cortical GABAergic neurons, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior. As such, this approach will accelerate the study of GABAergic circuits throughout the mammalian brain. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks.

              Gamma frequency oscillations are thought to provide a temporal structure for information processing in the brain. They contribute to cognitive functions, such as memory formation and sensory processing, and are disturbed in some psychiatric disorders. Fast-spiking, parvalbumin-expressing, soma-inhibiting interneurons have a key role in the generation of these oscillations. Experimental analysis in the hippocampus and the neocortex reveals that synapses among these interneurons are highly specialized. Computational analysis further suggests that synaptic specialization turns interneuron networks into robust gamma frequency oscillators.
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                Author and article information

                Journal
                9809671
                21092
                Nat Neurosci
                Nat. Neurosci.
                Nature neuroscience
                1097-6256
                1546-1726
                2 July 2013
                30 June 2013
                August 2013
                01 February 2014
                : 16
                : 8
                : 1068-1076
                Affiliations
                [1 ]Howard Hughes Medical Institute, University of California San Diego, La Jolla, California 92093-0634, USA
                [2 ]Center for Neural Circuits and Behavior, Neurobiology Section and Department of Neuroscience, University of California San Diego, La Jolla, California 92093-0634, USA
                [3 ]Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
                Author notes
                [# ]Correspondence should be addressed to: C.P. ( cpfeffer10@ 123456gmail.com ) or M.S. ( massimo@ 123456ucsd.edu )
                Article
                NIHMS486187
                10.1038/nn.3446
                3729586
                23817549
                f777cfad-c7e2-44f5-9aba-8810b68d3543

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                Neurosciences
                Neurosciences

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