title: Spatial memory deficits and motor coordination facilitation in cGMP-dependent protein kinase type II-deficient mice.
abstract: Activity-dependent trafficking of AMPA receptors to synapses regulates synaptic strength. Activation of the NMDA receptor induces several second messenger pathways that contribute to receptor trafficking-dependent plasticity, including the NO pathway, which elevates cGMP. In turn, cGMP activates the cGMP-dependent protein kinase type II (cGKII), which phosphorylates the AMPA receptor subunit GluA1 at serine 845, a critical step facilitating synaptic delivery in the mechanism of activity-dependent synaptic potentiation. Since cGKII is expressed in the striatum, amygdala, cerebral cortex, and hippocampus, it has been proposed that mice lacking cGKII may present phenotypic differences compared to their wild-type littermates in emotion-dependent tasks, learning and memory, and drug reward salience. Previous studies have shown that cGKII KO mice ingest higher amounts of ethanol as well as exhibit elevated anxiety levels compared to wild-type (WT) littermates. Here, we show that cGKII KO mice are significantly deficient in spatial learning while exhibiting facilitated motor coordination, demonstrating a clear dependence of memory-based tasks on cGKII. We also show diminished GluA1 phosphorylation in the postsynaptic density (PSD) of cGKII KO prefrontal cortex while in hippocampal PSD fractions, phosphorylation was not significantly altered. These data suggest that the role of cGKII may be more robust in particular brain regions, thereby impacting complex behaviors dependent on these regions differently.
authors.affiliation: Graduate Program in Neuroscience & Physiology, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Wincott
authors.forename: Seonil
authors.initials: S
authors.lastname: Kim
authors.forename: Roseann F
authors.initials: RF
authors.lastname: Titcombe
authors.forename: David S
authors.initials: DS
authors.lastname: Tukey
authors.forename: Hiwot K
authors.initials: HK
authors.lastname: Girma
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Pick
authors.forename: Loren M
authors.initials: LM
authors.lastname: Devito
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
authors.forename: Charles
authors.initials: C
authors.lastname: Hoeffer
authors.forename: Edward B
authors.initials: EB
authors.lastname: Ziff
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D057907:Post-Synaptic Density / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D045442:Rotarod Performance Test; D055139:Sensory Gating
chemical_list: D006152:Cyclic GMP; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D018091:Receptors, AMPA; C569730:Prkg2 protein, mouse