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      Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

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          SUMMARY

          The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca 2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information.

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          Most cited references53

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          A mesoscale connectome of the mouse brain.

          Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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            Dynamic predictions: oscillations and synchrony in top-down processing.

            Classical theories of sensory processing view the brain as a passive, stimulus-driven device. By contrast, more recent approaches emphasize the constructive nature of perception, viewing it as an active and highly selective process. Indeed, there is ample evidence that the processing of stimuli is controlled by top-down influences that strongly shape the intrinsic dynamics of thalamocortical networks and constantly create predictions about forthcoming sensory events. We discuss recent experiments indicating that such predictions might be embodied in the temporal structure of both stimulus-evoked and ongoing activity, and that synchronous oscillations are particularly important in this process. Coherence among subthreshold membrane potential fluctuations could be exploited to express selective functional relationships during states of expectancy or attention, and these dynamic patterns could allow the grouping and selection of distributed neuronal responses for further processing.
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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
                8809320
                1600
                Neuron
                Neuron
                Neuron
                0896-6273
                1097-4199
                30 November 2017
                17 May 2017
                10 December 2017
                : 94
                : 4
                : 891-907.e6
                Affiliations
                [1 ]Neurosciences Graduate Program, Stanford University, Stanford, CA 94305, USA
                [2 ]Electrical Engineering Graduate Program, Stanford University, Stanford, CA 94305, USA
                [3 ]Department of Biology, Stanford University, Stanford, CA 94305, USA
                [4 ]Department of Bioengineering, Stanford University, Stanford, CA 94305, USA
                [5 ]Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
                [6 ]Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA
                [7 ]Division of Biology and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA
                Author notes
                [* ]Correspondence: lluo@ 123456stanford.edu (L.L.), deissero@ 123456stanford.edu (K.D.)
                [8]

                These authors contributed equally

                [9]

                Lead Contact

                Article
                HHMIMS923712
                10.1016/j.neuron.2017.04.017
                5723385
                28521139
                39d1d7c6-bb4f-4ba2-9516-3e2acc0d41a9

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Neurosciences
                Neurosciences

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