Npas4 Regulates a Transcriptional Program in CA3 Required for Contextual Memory Formation

The rapid encoding of contextual memory requires the CA3 region of the hippocampus, but the necessary genetic pathways remain unclear. We found that the activity-dependent transcription factor Npas4 regulates a transcriptional program in CA3 that is required for contextual memory formation. Npas4 wa...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2011-12, Vol.334 (6063), p.1669-1675
Main Authors: Ramamoorthi, Kartik, Fropf, Robin, Belfort, Gabriel M., Fitzmaurice, Helen L., McKinney, Ross M., Neve, Rachael L., Otto, Tim, Lin, Yingxi
Format: Article
Language:English
Subjects:
Animal cognition
Animals
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Behavioral neuroscience
Biological and medical sciences
CA3 Region, Hippocampal - cytology
CA3 Region, Hippocampal - physiology
Chlorofluorocarbons
Conditioning, Psychological
Depolarization
DNA-directed RNA polymerase
Enhancer Elements, Genetic
Fear
Fundamental and applied biological sciences. Psychology
Gene Deletion
Gene expression
Gene Expression Regulation
Genes
Genes, Immediate-Early
Genetics
Hippocampus
knockout mutants
Learning
Memory
Messenger RNA
Mice
Mice, Knockout
Neurons
Neurons - physiology
Promoter regions
Promoter Regions, Genetic
RNA Polymerase II - metabolism
Rodents
transcription (genetics)
transcription factors
Transcription, Genetic
Transcriptional Activation
Transcriptional regulatory elements
Vertebrates: nervous system and sense organs
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Summary:The rapid encoding of contextual memory requires the CA3 region of the hippocampus, but the necessary genetic pathways remain unclear. We found that the activity-dependent transcription factor Npas4 regulates a transcriptional program in CA3 that is required for contextual memory formation. Npas4 was specifically expressed in CA3 after contextual learning. Global knockout or selective deletion of Npas4 in CA3 both resulted in impaired contextual memory, and restoration of Npas4 in CA3 was sufficient to reverse the deficit in global knockout mice. By recruiting RNA polymerase II to promoters and enhancers of target genes, Npas4 regulates a learning-specific transcriptional program in CA3 that includes many well-known activity-regulated genes, which suggests that Npas4 is a master regulator of activity-regulated gene programs and is central to memory formation.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1208049