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      Using the Morris Water Maze to Assess Spatial Learning and Memory in Weanling Mice

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      PLoS ONE
      Public Library of Science

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          Abstract

          Mouse models have been indispensable for elucidating normal and pathological processes that influence learning and memory. A widely used method for assessing these cognitive processes in mice is the Morris water maze, a classic test for examining spatial learning and memory. However, Morris water maze studies with mice have principally been performed using adult animals, which preclude studies of critical neurodevelopmental periods when the cellular and molecular substrates of learning and memory are formed. While weanling rats have been successfully trained in the Morris water maze, there have been few attempts to test weanling mice in this behavioral paradigm even though mice offer significant experimental advantages because of the availability of many genetically modified strains. Here, we present experimental evidence that weanling mice can be trained in the Morris water maze beginning on postnatal day 24. Maze-trained weanling mice exhibit significant improvements in spatial learning over the training period and results of the probe trial indicate the development of spatial memory. There were no sex differences in the animals’ performance in these tasks. In addition, molecular biomarkers of synaptic plasticity are upregulated in maze-trained mice at the transcript level. These findings demonstrate that the Morris water maze can be used to assess spatial learning and memory in weanling mice, providing a potentially powerful experimental approach for examining the influence of genes, environmental factors and their interactions on the development of learning and memory.

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          Most cited references52

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          Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.

          Arc/Arg3.1 is robustly induced by plasticity-producing stimulation and specifically targeted to stimulated synaptic areas. To investigate the role of Arc/Arg3.1 in synaptic plasticity and learning and memory, we generated Arc/Arg3.1 knockout mice. These animals fail to form long-lasting memories for implicit and explicit learning tasks, despite intact short-term memory. Moreover, they exhibit a biphasic alteration of hippocampal long-term potentiation in the dentate gyrus and area CA1 with an enhanced early and absent late phase. In addition, long-term depression is significantly impaired. Together, these results demonstrate a critical role for Arc/Arg3.1 in the consolidation of enduring synaptic plasticity and memory storage.
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            New views of Arc, a master regulator of synaptic plasticity.

            Many proteins have been implicated in synaptic and experience-dependent plasticity. However, few demonstrate the exquisite regulation of expression and breadth of functional importance as the immediate early gene product Arc. Here we review and attempt to synthesize the disparate views of Arc in neuronal function. The main conclusion garnered from this body of work is that Arc is a critical effector molecule downstream of many molecular signaling pathways and that dysregulation of Arc expression can have dire consequences for normal brain function.
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              Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.

              Homer is a neuronal immediate early gene (IEG) that is enriched at excitatory synapses and binds group 1 metabotropic glutamate receptors (mGluRs). Here, we characterize a family of Homer-related proteins derived from three distinct genes. Like Homer IEG (now termed Homer 1a), all new members bind group 1 mGluRs. In contrast to Homer 1a, new members are constitutively expressed and encode a C-terminal coiled-coil (CC) domain that mediates self-multimerization. CC-Homers form natural complexes that cross-link mGluRs and are enriched at the postsynaptic density. Homer 1a does not multimerize and blocks the association of mGluRs with CC-Homer complexes. These observations support a model in which the dynamic expression of Homer 1a competes with constitutively expressed CC-Homers to modify synaptic mGluR properties.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                17 April 2015
                2015
                : 10
                : 4
                : e0124521
                Affiliations
                [001]Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America
                Université Pierre et Marie Curie, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: CDB DY PJL. Performed the experiments: CDB DY. Analyzed the data: CDB DY PJL. Wrote the paper: CDB DY PJL.

                Article
                PONE-D-15-03461
                10.1371/journal.pone.0124521
                4401674
                25886563
                f149c27b-aac8-4eb3-808e-fdced33f01b0
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 23 January 2015
                : 16 March 2015
                Page count
                Figures: 4, Tables: 2, Pages: 16
                Funding
                This work was supported by the United States National Institutes of Health (grant R01 ES014901 to PJL); CDB was supported by predoctoral fellowships provided by grants P42 ES04699 and T32 ES007059 and by a scholarship from the Achievement Rewards for College Scientists (ARCS) Foundation ( https://www.arcsfoundation.org/). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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