title: Increased prefrontal cortex neurogranin enhances plasticity and extinction learning.
abstract: Increasing plasticity in neurons of the prefrontal cortex (PFC) has been proposed as a possible therapeutic tool to enhance extinction, a process that is impaired in post-traumatic stress disorder, schizophrenia, and addiction. To test this hypothesis, we generated transgenic mice that overexpress neurogranin (a calmodulin-binding protein that facilitates long-term potentiation) in the PFC. Neurogranin overexpression in the PFC enhanced long-term potentiation and increased the rates of extinction learning of both fear conditioning and sucrose self-administration. Our results indicate that elevated neurogranin function within the PFC can enhance local plasticity and increase the rate of extinction learning across different behavioral tasks. Thus, neurogranin can provide a molecular link between enhanced plasticity and enhanced extinction.
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Joshua
authors.initials: J
authors.lastname: Brown
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Audra
authors.identifier: http://orcid.org/0000-0003-2138-7673
authors.initials: A
authors.lastname: Kramer
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Kanwardeep
authors.initials: K
authors.lastname: Kaleka
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Amber
authors.identifier: http://orcid.org/0000-0003-2370-4767
authors.initials: A
authors.lastname: Petersen
authors.affiliation: Molecular & Behavioral Neuroscience Institute and.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Krueger
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and.
authors.forename: Matthew
authors.initials: M
authors.lastname: Florence
authors.affiliation: Neuroscience Research Center, and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin 53132.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Muelbl
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy.
authors.forename: Michelle
authors.initials: M
authors.lastname: Battle
authors.affiliation: Molecular & Behavioral Neuroscience Institute and Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Geoffrey G
authors.initials: GG
authors.lastname: Murphy
authors.affiliation: Neuroscience Research Center, and Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin 53132.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Olsen
authors.affiliation: Departments of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center, and ngerges@mcw.edu.
authors.forename: Nashaat Z
authors.initials: NZ
authors.lastname: Gerges
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology; D004558:Electric Stimulation; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051579:Neurogranin / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics*; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D051579:Neurogranin; D013395:Sucrose; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
keywords: CaMKII; calmodulin; extinction; neurogranin; prefrontal cortex