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      The hippocampal CA2 region is essential for social memory

      1 , 1 , 2

      Nature

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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 references 47

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          A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

          The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universal responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in a number of Cre-driver lines, including novel Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.
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            Millisecond-timescale, genetically targeted optical control of neural activity.

            Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.
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              Morris water maze: procedures for assessing spatial and related forms of learning and memory.

              The Morris water maze (MWM) is a test of spatial learning for rodents that relies on distal cues to navigate from start locations around the perimeter of an open swimming arena to locate a submerged escape platform. Spatial learning is assessed across repeated trials and reference memory is determined by preference for the platform area when the platform is absent. Reversal and shift trials enhance the detection of spatial impairments. Trial-dependent, latent and discrimination learning can be assessed using modifications of the basic protocol. Search-to-platform area determines the degree of reliance on spatial versus non-spatial strategies. Cued trials determine whether performance factors that are unrelated to place learning are present. Escape from water is relatively immune from activity or body mass differences, making it ideal for many experimental models. The MWM has proven to be a robust and reliable test that is strongly correlated with hippocampal synaptic plasticity and NMDA receptor function. We present protocols for performing variants of the MWM test, from which results can be obtained from individual animals in as few as 6 days.
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                Author and article information

                Journal
                0410462
                6011
                Nature
                Nature
                Nature
                0028-0836
                1476-4687
                7 April 2014
                23 February 2014
                3 April 2014
                03 October 2014
                : 508
                : 7494
                : 88-92
                Affiliations
                [1 ]Department of Neuroscience, Kavli Institute, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Dr. New York, NY 10032
                [2 ]Department of Pharmacology, Kavli Institute, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University 1051 Riverside Dr. New York, NY 10032
                Author notes
                Address correspondence to: sas8@ 123456columbia.edu
                Article
                NIHMS555416
                10.1038/nature13028
                4000264
                24572357

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