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      Detecting and discriminating novel objects: The impact of perirhinal cortex disconnection on hippocampal activity patterns

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          ABSTRACT

          Perirhinal cortex provides object‐based information and novelty/familiarity information for the hippocampus. The necessity of these inputs was tested by comparing hippocampal c‐ fos expression in rats with or without perirhinal lesions. These rats either discriminated novel from familiar objects (Novel‐Familiar) or explored pairs of novel objects (Novel‐Novel). Despite impairing Novel‐Familiar discriminations, the perirhinal lesions did not affect novelty detection, as measured by overall object exploration levels (Novel‐Novel condition). The perirhinal lesions also largely spared a characteristic network of linked c‐ fos expression associated with novel stimuli (entorhinal cortex→CA3→distal CA1→proximal subiculum). The findings show: I) that perirhinal lesions preserve behavioral sensitivity to novelty, whilst still impairing the spontaneous ability to discriminate novel from familiar objects, II) that the distinctive patterns of hippocampal c‐ fos activity promoted by novel stimuli do not require perirhinal inputs, III) that entorhinal Fos counts (layers II and III) increase for novelty discriminations, IV) that hippocampal c‐ fos networks reflect proximal‐distal connectivity differences, and V) that discriminating novelty creates different pathway interactions from merely detecting novelty, pointing to top‐down effects that help guide object selection. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

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          Optogenetic stimulation of a hippocampal engram activates fear memory recall

          A specific memory is thought to be encoded by a sparse population of neurons 1,2 . These neurons can be tagged during learning for subsequent identification 3 and manipulation 4,5,6 . Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, a critical question of sufficiency remains: can one elicit the behavioral output of a specific memory by directly activating a population of neurons that was active during learning? Here we show that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behavior. We labeled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) 7,8 and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear conditioned mice with cells labeled by EYFP instead of ChR2. Finally, activation of cells labeled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context-specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
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            Interplay of hippocampus and prefrontal cortex in memory.

            Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Recognition memory: what are the roles of the perirhinal cortex and hippocampus?

              The hallmark of medial temporal lobe amnesia is a loss of episodic memory such that patients fail to remember new events that are set in an autobiographical context (an episode). A further symptom is a loss of recognition memory. The relationship between these two features has recently become contentious. Here, we focus on the central issue in this dispute--the relative contributions of the hippocampus and the perirhinal cortex to recognition memory. A resolution is vital not only for uncovering the neural substrates of these key aspects of memory, but also for understanding the processes disrupted in medial temporal lobe amnesia and the validity of animal models of this syndrome.
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                Author and article information

                Contributors
                KinnavaneL@cardiff.ac.uk
                Journal
                Hippocampus
                Hippocampus
                10.1002/(ISSN)1098-1063
                HIPO
                Hippocampus
                John Wiley and Sons Inc. (Hoboken )
                1050-9631
                1098-1063
                22 July 2016
                November 2016
                : 26
                : 11 ( doiID: 10.1002/hipo.v26.11 )
                : 1393-1413
                Affiliations
                [ 1 ] School of PsychologyCardiff University 70 Park Place, Cardiff Wales CF10 3ATUnited Kingdom
                [ 2 ]Present address: Cristian M. Olarte‐Sánchez is currently at Rowett Institute of Nutrition and Health, Institute of Medical Sciences, Aberdeen University, Foresterhill Aberdeen AB25 2ZDUK
                Author notes
                [*] [* ]Correspondence to: Lisa Kinnavane, Cardiff University, School of Psychology, Cardiff University, Tower Building, 70 Park Place, Cardiff, CF10 3AT, United Kingdom. E‐mail: KinnavaneL@ 123456cardiff.ac.uk
                Article
                HIPO22615
                10.1002/hipo.22615
                5082501
                27398938
                d6f0eda5-af0e-4e90-a0f2-71e80a4d56e5
                © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 June 2016
                Page count
                Figures: 9, Tables: 1, Pages: 21, Words: 14549
                Funding
                Funded by: Wellcome Trust
                Award ID: WT087955
                Award ID: WT09520
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                hipo22615
                November 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.6 mode:remove_FC converted:27.10.2016

                Neurology
                entorhinal cortex,hippocampus,nucleus reuniens,prefrontal cortex,recognition memory
                Neurology
                entorhinal cortex, hippocampus, nucleus reuniens, prefrontal cortex, recognition memory

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