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      Hippocampal-prefrontal input supports spatial encoding in working memory

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          Summary

          Spatial working memory, the caching of behaviorally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. While the prefrontal cortex and hippocampus are known to jointly contribute to successful spatial working memory, the anatomical pathway and temporal window for interaction of these structures critical to spatial working memory has not yet been established. Here, we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory.

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          Most cited references36

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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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            Cellular basis of working memory

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              The importance of mixed selectivity in complex cognitive tasks.

              Single-neuron activity in the prefrontal cortex (PFC) is tuned to mixtures of multiple task-related aspects. Such mixed selectivity is highly heterogeneous, seemingly disordered and therefore difficult to interpret. We analysed the neural activity recorded in monkeys during an object sequence memory task to identify a role of mixed selectivity in subserving the cognitive functions ascribed to the PFC. We show that mixed selectivity neurons encode distributed information about all task-relevant aspects. Each aspect can be decoded from the population of neurons even when single-cell selectivity to that aspect is eliminated. Moreover, mixed selectivity offers a significant computational advantage over specialized responses in terms of the repertoire of input-output functions implementable by readout neurons. This advantage originates from the highly diverse nonlinear selectivity to mixtures of task-relevant variables, a signature of high-dimensional neural representations. Crucially, this dimensionality is predictive of animal behaviour as it collapses in error trials. Our findings recommend a shift of focus for future studies from neurons that have easily interpretable response tuning to the widely observed, but rarely analysed, mixed selectivity neurons.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                30 March 2015
                08 June 2015
                18 June 2015
                18 December 2015
                : 522
                : 7556
                : 309-314
                Affiliations
                [1 ]Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032 USA
                [2 ]Department of Psychiatry, Columbia University
                [3 ]Department of Neuroscience, Columbia University
                [4 ]Physical Sciences Department, T. J. Watson Research Center, IBM 1101 Kitchawan Rd, Yorktown Heights, NY 10598, USA
                [5 ]Italian Academy for Advanced Studies in America, Columbia University
                [6 ]Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA
                [7 ]Center for Neuroscience, Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15213, USA
                [8 ]Kavli Institute for Brain Sciences, Columbia University
                [9 ]Division of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032 USA
                Author notes
                Corresponding author: Joshua Gordon ( jg343@ 123456columbia.edu )
                Article
                NIHMS675681
                10.1038/nature14445
                4505751
                26053122
                060376fc-a6ee-43e8-acec-ce511aa69d77
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