title: cGMP-dependent protein kinase type II knockout mice exhibit working memory impairments, decreased repetitive behavior, and increased anxiety-like traits.
abstract: 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.
authors.affiliation: Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States. Electronic address: cmw396@nyu.edu.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Wincott
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Sinedu
authors.initials: S
authors.lastname: Abera
authors.affiliation: The Ohio State University, Departments of Psychology and Neuroscience, Columbus, OH 43210, United States.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Vunck
authors.affiliation: Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Natasha
authors.initials: N
authors.lastname: Tirko
authors.affiliation: Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Roseann F
authors.initials: RF
authors.lastname: Titcombe
authors.affiliation: Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Shannon O
authors.initials: SO
authors.lastname: Antoine
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Tukey
authors.affiliation: Center for Memory and Brain, Boston University, Boston, MA 02215, United States.
authors.forename: Loren M
authors.initials: LM
authors.lastname: DeVito
authors.affiliation: Technical University of Munich, Biedersteiner Str. 29, 80802 Munich, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: 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.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Hoeffer
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology*; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000235:genetics* / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation
chemical_list: D062967:Cyclic GMP-Dependent Protein Kinase Type II
keywords: AMPA receptors; Anxiety; Learning; Memory; Plasticity
references.citation: J Psychopharmacol. 2007 Mar;21(2):134-5
references.pmid: 17329288
references.citation: Psychopharmacology (Berl). 2009 Jun;204(2):361-73
references.pmid: 19189082
references.citation: J Neurophysiol. 1973 Jan;36(1):61-78
references.pmid: 4196203
references.citation: Trends Cogn Sci. 2007 Jul;11(7):307-16
references.pmid: 17553730
references.citation: Nat Neurosci. 2000 Jan;3(1):85-90
references.pmid: 10607400
references.citation: Curr Mol Med. 2002 Nov;2(7):639-47
references.pmid: 12420803
references.citation: Neuron. 1996 Jun;16(6):1179-88
references.pmid: 8663994
references.citation: Brain Res Cogn Brain Res. 1999 Oct 25;8(3):299-310
references.pmid: 10556607
references.citation: Psychopharmacology (Berl). 1982;78(4):368-72
references.pmid: 6818600
references.citation: Conscious Cogn. 2003 Mar;12(1):83-139
references.pmid: 12617864
references.citation: Prog Brain Res. 1990;85:325-35; discussion 335-6
references.pmid: 2094903
references.citation: Eur J Neurosci. 2004 Dec;20(12):3498-506
references.pmid: 15610182
references.citation: Science. 2008 Jul 18;321(5887):421-2
references.pmid: 18635808
references.citation: Biochim Biophys Acta. 2013 Aug;1833(8):1820-31
references.pmid: 23545413
references.citation: Methods Find Exp Clin Pharmacol. 2005 Dec;27(10):685-7
references.pmid: 16395417
references.citation: Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jun 3;43:7-13
references.pmid: 23220093
references.citation: Neuron. 2009 Feb 12;61(3):340-50
references.pmid: 19217372
references.citation: Cereb Cortex. 1996 Jul-Aug;6(4):600-11
references.pmid: 8670685
references.citation: Behav Brain Res. 2012 Dec 1;235(2):287-92
references.pmid: 22921929
references.citation: Behav Neurosci. 1998 Apr;112(2):293-303
references.pmid: 9588479
references.citation: J Learn Disabil. 2011 Jan-Feb;44(1):3-17
references.pmid: 20375288
references.citation: Jpn J Pharmacol. 1995 May;68(1):65-70
references.pmid: 7494384
references.citation: Cereb Cortex. 1996 May-Jun;6(3):470-81
references.pmid: 8670672
references.citation: Neuron. 2006 Jul 20;51(2):213-25
references.pmid: 16846856
references.citation: Brain Res. 1997 Aug 8;765(1):37-50
references.pmid: 9310392
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Dec 27;365(1560):4021-8
references.pmid: 21078654
references.citation: J Cogn Neurosci. 1992 Summer;4(3):281-8
references.pmid: 23964884
references.citation: Biol Psychiatry. 2008 Nov 15;64(10):863-70
references.pmid: 18639237
references.citation: Br J Pharmacol. 1978 Jan;62(1):19-24
references.pmid: 563752
references.citation: Trends Cogn Sci. 2012 Jan;16(1):43-51
references.pmid: 22138231
references.citation: Neuron. 2007 Nov 21;56(4):670-88
references.pmid: 18031684
references.citation: Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13468-72
references.pmid: 8942958
references.citation: Ann N Y Acad Sci. 1995 Dec 15;769:151-9
references.pmid: 8595022
references.citation: Annu Rev Neurosci. 2002;25:103-26
references.pmid: 12052905
references.citation: Neurosci Biobehav Rev. 1999 Nov;23(7):925-35
references.pmid: 10580307
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 4;109(49):19900-9
references.pmid: 23086162
references.citation: J Neurosci. 2003 Nov 5;23(31):9987-95
references.pmid: 14602812
references.citation: Comp Med. 2011 Apr;61(2):119-30
references.pmid: 21535922
references.citation: Neurosci Lett. 2010 Mar 3;471(2):63-5
references.pmid: 20036313
references.citation: Behav Brain Res. 2003 Dec 17;147(1-2):107-14
references.pmid: 14659576
references.citation: Nat Protoc. 2006;1(3):1117-9
references.pmid: 17406392
references.citation: C R Acad Sci III. 1998 Feb-Mar;321(2-3):167-73
references.pmid: 9759336
references.citation: J Neurosci. 2000 Dec 15;20(24):9272-6
references.pmid: 11125005
references.citation: Neurobiol Learn Mem. 2013 Jan;99:32-7
references.pmid: 23103773
references.citation: Annu Rev Neurosci. 1994;17:31-108
references.pmid: 8210177
references.citation: Physiol Behav. 1998 Jun 1;64(3):373-80
references.pmid: 9748107
references.citation: Eur J Pharmacol. 1986 Jul 31;126(3):223-9
references.pmid: 2875886
references.citation: Neurosci Res. 1994 Nov;21(1):1-11
references.pmid: 7708289
references.citation: Annu Rev Physiol. 1995;57:683-706
references.pmid: 7539993
references.citation: Cell. 2003 Mar 7;112(5):631-43
references.pmid: 12628184
references.citation: Neural Plast. 2007;2007:52087
references.pmid: 18288249
references.citation: Behav Brain Res. 1989 Dec 1;35(3):221-40
references.pmid: 2688683
references.citation: Behav Genet. 2012 Sep;42(5):830-44
references.pmid: 22573112
references.citation: J Neuropsychiatry Clin Neurosci. 1997 Fall;9(4):568-73
references.pmid: 9447498
references.citation: Neuropsychopharmacology. 2008 Sep;33(10):2474-82
references.pmid: 18033234
references.citation: J Neurosci. 1997 Mar 1;17(5):1880-90
references.pmid: 9030646
references.citation: Science. 1996 Dec 20;274(5295):2082-6
references.pmid: 8953039
references.citation: Science. 2013 Jun 7;340(6137):1243-6
references.pmid: 23744950
references.citation: Psychopharmacology (Berl). 2014 Jun;231(11):2291-8
references.pmid: 24402133
references.citation: Neuropsychopharmacology. 2012 Apr;37(5):1305-20
references.pmid: 22189291
references.citation: Hippocampus. 2004;14(2):216-23
references.pmid: 15098726
references.citation: Behav Neurosci. 2001 Dec;115(6):1204-11
references.pmid: 11770052
references.citation: Biol Psychiatry. 2003 Jan 1;53(1):25-38
references.pmid: 12513942
references.citation: Neural Plast. 2007;2007:75617
references.pmid: 17728839
references.citation: J Neurosci. 1999 Jan 1;19(1):48-55
references.pmid: 9870937