Impaired Synaptic Plasticity and cAMP Response Element-Binding Protein Activation in Ca 2+ /Calmodulin-Dependent Protein Kinase Type IV/Gr-Deficient Mice – ScienceOpen
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      Impaired Synaptic Plasticity and cAMP Response Element-Binding Protein Activation in Ca 2+/Calmodulin-Dependent Protein Kinase Type IV/Gr-Deficient Mice

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          Abstract

          The Ca 2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a key effector of neuronal Ca 2+ signaling; its function was analyzed by targeted gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neuronal cAMP-responsive element binding protein (CREB) phosphorylation and Ca 2+/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neurons and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These results support an important role for CaMKIV/Gr in Ca 2+-regulated neuronal gene transcription and synaptic plasticity and suggest that the contribution of other signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mice.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          1 September 2000
          : 20
          : 17
          : 6459-6472
          Affiliations
          [ 1 ]Departments of Pediatrics,
          [ 2 ]Anesthesiology, Anatomy and Neurobiology,
          [ 3 ]Psychiatry,
          [ 4 ]Neurology, and the Center for the Study of Nervous System Injury,
          [ 5 ]Molecular Biology and Pharmacology and Obstetrics and Gynecology, and
          [ 6 ]Pathology and Immunology, and the Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110,
          [ 7 ]Division of Immunology/Rheumatology, The Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, and
          [ 8 ]Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
          Article
          PMC6772951 PMC6772951 6772951 4489
          10.1523/JNEUROSCI.20-17-06459.2000
          6772951
          10964952
          cdbb1e48-df0c-4e62-bb38-ca00bcbc041c
          Copyright © 2000 Society for Neuroscience
          History
          : 21 January 2000
          : 1 May 2000
          : 22 June 2000
          Categories
          ARTICLE
          Cellular/Molecular
          Custom metadata
          5.00

          memory,CREB,LTD,LTP,synaptic plasticity,calcium/calmodulin-dependent kinase

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