title: Prefrontal consolidation supports the attainment of fear memory accuracy.
abstract: The neural mechanisms underlying the attainment of fear memory accuracy for appropriate discriminative responses to aversive and nonaversive stimuli are unclear. Considerable evidence indicates that coactivator of transcription and histone acetyltransferase cAMP response element binding protein (CREB) binding protein (CBP) is critically required for normal neural function. CBP hypofunction leads to severe psychopathological symptoms in human and cognitive abnormalities in genetic mutant mice with severity dependent on the neural locus and developmental time of the gene inactivation. Here, we showed that an acute hypofunction of CBP in the medial prefrontal cortex (mPFC) results in a disruption of fear memory accuracy in mice. In addition, interruption of CREB function in the mPFC also leads to a deficit in auditory discrimination of fearful stimuli. While mice with deficient CBP/CREB signaling in the mPFC maintain normal responses to aversive stimuli, they exhibit abnormal responses to similar but nonrelevant stimuli when compared to control animals. These data indicate that improvement of fear memory accuracy involves mPFC-dependent suppression of fear responses to nonrelevant stimuli. Evidence from a context discriminatory task and a newly developed task that depends on the ability to distinguish discrete auditory cues indicated that CBP-dependent neural signaling within the mPFC circuitry is an important component of the mechanism for disambiguating the meaning of fear signals with two opposing values: aversive and nonaversive.
authors.affiliation: Department of Psychology and Neuroscience Program, University of California Riverside, California 92521, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Vieira
authors.affiliation: Department of Psychology and Neuroscience Program, University of California Riverside, California 92521, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lovelace
authors.affiliation: Biomedical Sciences Program, University of California Riverside, California 92521, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Corches
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Asim J
authors.initials: AJ
authors.lastname: Rashid
authors.affiliation: Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
authors.forename: Sheena A
authors.initials: SA
authors.lastname: Josselyn
authors.affiliation: Department of Psychology and Neuroscience Program, University of California Riverside, California 92521, USA Biomedical Sciences Program, University of California Riverside, California 92521, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Korzus
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D004192:Discrimination, Psychological / Q000502:physiology*; D004597:Electroshock; D005239:Fear / Q000502:physiology*; D005528:Foot; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse