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      The hippocampal CA2 region is essential for social memory

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      Nature
      Springer Science and Business Media LLC

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          Abstract

          Summary The hippocampus is critical for encoding declarative memory, our repository of knowledge of who, what, where, and when 1 . Mnemonic information is processed in the hippocampus through several parallel routes involving distinct subregions. In the classic trisynaptic pathway, information proceeds from entorhinal cortex (EC) to dentate gyrus (DG) to CA3 and then to CA1, the main hippocampal output 2 . Genetic lesions of EC 3 and hippocampal DG 4 , CA3 5 , and CA1 6 regions have revealed their distinct functions in learning and memory. In contrast, little is known about the role of CA2, a relatively small area interposed between CA3 and CA1 that forms the nexus of a powerful disynaptic circuit linking EC input with CA1 output 7 . Here, we report a novel transgenic mouse line that enabled us to selectively examine the synaptic connections and behavioral role of the CA2 region in adult mice. Genetically targeted inactivation of CA2 pyramidal neurons caused a pronounced loss of social memory, the ability of an animal to remember a conspecific, with no change in sociability or several other hippocampal-dependent behaviors, including spatial and contextual memory. These behavioral and anatomical results thus reveal CA2 as a critical hub of sociocognitive memory processing.

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          Most cited references35

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          The essential role of hippocampal CA1 NMDA receptor-dependent synaptic plasticity in spatial memory.

          We have produced a mouse strain in which the deletion of the NMDAR1 gene is restricted to the CA1 pyramidal cells of the hippocampus by using a new and general method that allows CA1-restricted gene knockout. The mutant mice grow into adulthood without obvious abnormalities. Adult mice lack NMDA receptor-mediated synaptic currents and long-term potentiation in the CA1 synapses and exhibit impaired spatial memory but unimpaired nonspatial learning. Our results strongly suggest that activity-dependent modifications of CA1 synapses, mediated by NMDA receptors, play an essential role in the acquisition of spatial memories.
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            Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion.

            Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks after functional integration into the neuronal network, distinguishing them from less active, older adult-born GCs and the major population of dentate GCs generated developmentally. To ascertain whether young and old GCs perform distinct memory functions, we created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts, which was reduced following ablation of young GCs. Furthermore, these mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation requires adult-born young GCs but not old GCs, and older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion. Copyright © 2012 Elsevier Inc. All rights reserved.
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              The cognitive neuroscience of human memory since H.M.

              Work with patient H.M., beginning in the 1950s, established key principles about the organization of memory that inspired decades of experimental work. Since H.M., the study of human memory and its disorders has continued to yield new insights and to improve understanding of the structure and organization of memory. Here we review this work with emphasis on the neuroanatomy of medial temporal lobe and diencephalic structures important for memory, multiple memory systems, visual perception, immediate memory, memory consolidation, the locus of long-term memory storage, the concepts of recollection and familiarity, and the question of how different medial temporal lobe structures may contribute differently to memory functions.
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                Author and article information

                Journal
                Nature
                Nature
                Springer Science and Business Media LLC
                0028-0836
                1476-4687
                April 2014
                February 23 2014
                April 2014
                : 508
                : 7494
                : 88-92
                Article
                10.1038/nature13028
                c5cec2e3-ad89-4f7a-b478-12a0d5306dd3
                © 2014

                http://www.springer.com/tdm

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