cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.

Autor: Wincott CM; Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States. Electronic address: cmw396@nyu.edu., Abera S; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States., Vunck SA; The Ohio State University, Departments of Psychology and Neuroscience, Columbus, OH 43210, United States., Tirko N; Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States., Choi Y; Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, United States., Titcombe RF; Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States., Antoine SO; Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States., Tukey DS; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States., DeVito LM; Center for Memory and Brain, Boston University, Boston, MA 02215, United States., Hofmann F; Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany., Hoeffer CA; Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, United States; Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80303, United States., Ziff EB; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States.
Jazyk: angličtina
Zdroj: Neurobiology of learning and memory [Neurobiol Learn Mem] 2014 Oct; Vol. 114, pp. 32-9. Date of Electronic Publication: 2014 Apr 18.
DOI: 10.1016/j.nlm.2014.04.007
Abstrakt: Neuronal activity regulates AMPA receptor trafficking, a process that mediates changes in synaptic strength, a key component of learning and memory. This form of plasticity may be induced by stimulation of the NMDA receptor which, among its activities, increases cyclic guanosine monophosphate (cGMP) through the nitric oxide synthase pathway. cGMP-dependent protein kinase type II (cGKII) is ultimately activated via this mechanism and AMPA receptor subunit GluA1 is phosphorylated at serine 845. This phosphorylation contributes to the delivery of GluA1 to the synapse, a step that increases synaptic strength. Previous studies have shown that cGKII-deficient mice display striking spatial learning deficits in the Morris Water Maze compared to wild-type littermates as well as lowered GluA1 phosphorylation in the postsynaptic density of the prefrontal cortex (Serulle et al., 2007; Wincott et al., 2013). In the current study, we show that cGKII knockout mice exhibit impaired working memory as determined using the prefrontal cortex-dependent Radial Arm Maze (RAM). Additionally, we report reduced repetitive behavior in the Marble Burying task (MB), and heightened anxiety-like traits in the Novelty Suppressed Feeding Test (NSFT). These data suggest that cGKII may play a role in the integration of information that conveys both anxiety-provoking stimuli as well as the spatial and environmental cues that facilitate functional memory processes and appropriate behavioral response.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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