title: Targeted deletion of AKAP7 in dentate granule cells impairs spatial discrimination.
abstract: Protein Kinase A (PKA) mediates synaptic plasticity and is widely implicated in learning and memory. The hippocampal dentate gyrus (DG) is thought to be responsible for processing and encoding distinct contextual associations in response to highly similar inputs. The mossy fiber (MF) axons of the dentate granule cells convey strong excitatory drive to CA3 pyramidal neurons and express presynaptic, PKA-dependent forms of plasticity. Here, we demonstrate an essential role for the PKA anchoring protein, AKAP7, in mouse MF axons and terminals. Genetic ablation of AKAP7 specifically from dentate granule cells results in disruption of MF-CA3 LTP directly initiated by cAMP, and the AKAP7 mutant mice are selectively deficient in pattern separation behaviors. Our results suggest that the AKAP7/PKA complex in the MF projections plays an essential role in synaptic plasticity and contextual memory formation.
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Jones
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Deem
authors.affiliation: Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Younts
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Michael
authors.initials: M
authors.lastname: Weisenhaus
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Sanford
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Slack
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Jenesa
authors.initials: J
authors.lastname: Chin
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nachmanson
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: McKennon
authors.affiliation: Dominick P Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, United States.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Castillo
authors.affiliation: Department of Pharmacology, University of Washington School of Medicine, Seattle, United States.
authors.forename: G Stanley
authors.identifier: 0000-0001-9531-2936
authors.initials: GS
authors.lastname: McKnight
mesh_terms: D054758:A Kinase Anchor Proteins / Q000172:deficiency*; D000818:Animals; D056654:CA3 Region, Hippocampal / Q000502:physiology*; D002529:Cerebellar Nuclei / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D055786:Gene Knockout Techniques; D051379:Mice; D019599:Mossy Fibers, Hippocampal / Q000502:physiology*; D013037:Spatial Behavior
chemical_list: D054758:A Kinase Anchor Proteins; C487791:Akap7 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: PKA anchoring; mouse; neuroscience; spatial discrimination; synaptic plasticity