Publication Date:
2011-12-24
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038289/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038289/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ramamoorthi, Kartik -- Fropf, Robin -- Belfort, Gabriel M -- Fitzmaurice, Helen L -- McKinney, Ross M -- Neve, Rachael L -- Otto, Tim -- Lin, Yingxi -- MH091220-01/MH/NIMH NIH HHS/ -- R01 MH091220/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2011 Dec 23;334(6063):1669-75. doi: 10.1126/science.1208049.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22194569" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic Helix-Loop-Helix Transcription Factors/*genetics/*metabolism
;
CA3 Region, Hippocampal/cytology/*physiology
;
Conditioning (Psychology)
;
Enhancer Elements, Genetic
;
Fear
;
Gene Deletion
;
*Gene Expression Regulation
;
Genes, Immediate-Early
;
Learning
;
*Memory
;
Mice
;
Mice, Knockout
;
Neurons/physiology
;
Promoter Regions, Genetic
;
RNA Polymerase II/metabolism
;
*Transcription, Genetic
;
Transcriptional Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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