CBP-Dependent memory consolidation in the prefrontal cortex supports object-location learning.
Recognition of an object's location in space is supported by hippocampus-dependent recollection. Converging evidence strongly suggests that the interplay between the prefrontal cortex and hippocampus is critical for spatial memory. Lesion, pharmacological, and genetic studies have been successful in dissecting the role of plasticity in the hippocampal circuit in a variety of neural processes relevant to spatial memory, including memory for the location of objects. However, prefrontal mechanisms underlying spatial memory are less well understood. Here, we show that an acute hypofunction of the cyclic-AMP regulatory element binding protein (CREB) Binding Protein (CBP) histone acetyltransferase (HAT) in the medial prefrontal cortex (mPFC) results in delay-dependent disruption of object-location memory. These data suggest that mechanisms involving CBP HAT-mediated lysine acetylation of nuclear proteins support selectively long-term encoding in the mPFC circuits. Evidence from the object-location task suggests that long-term memory encoding within the mPFC complements hippocampus-dependent spatial memory mechanisms and may be critical for broader network integration of information necessary for an assessment of subtle spatial differences to guide appropriate behavioral response during retrieval of spatial memories.
Department of Psychology & Neuroscience Program, University of California Riverside, California.
Philip A
PA
Vieira
Department of Psychology & Neuroscience Program, University of California Riverside, California.
Edward
E
Korzus
D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D000069077:Memory Consolidation / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000166:cytology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D065853:Spatial Learning / Q000502:physiology*; D065852:Spatial Memory / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D051548:Histone Acetyltransferases
epigenetic regulation; histone acetyltransferase; mPFC; object-location; spatial memory