BBB Major Publications

Document Type

Journal Article

Date of this Version

10-1-2012

Publication Source

The Journal of Clinical Investigation

Volume

122

Issue

10

Start Page

3593

Last Page

3602

DOI

10.1172/JCI64145

Abstract

The formation of a long-lasting memory requires a transcription-dependent consolidation period that converts a short-term memory into a long-term memory. Nuclear receptors compose a class of transcription factors that regulate diverse biological processes, and several nuclear receptors have been implicated in memory formation. Here, we examined the potential contribution of nuclear receptors to memory consolidation by measuring the expression of all 49 murine nuclear receptors after learning. We identified 13 nuclear receptors with increased expression after learning, including all 3 members of the Nr4a subfamily. These CREB-regulated Nr4a genes encode ligand-independent “orphan” nuclear receptors. We found that blocking NR4A activity in memory-supporting brain regions impaired long-term memory but did not impact short-term memory in mice. Further, expression of Nr4a genes increased following the memory-enhancing effects of histone deacetylase (HDAC) inhibitors. Blocking NR4A signaling interfered with the ability of HDAC inhibitors to enhance memory. These results demonstrate that the Nr4a gene family contributes to memory formation and is a promising target for improving cognitive function.

Copyright/Permission Statement

Originally published in the Journal of Clinical Investigation by the American Society for Clinical Investigation (ASCI). Reproduced with permission.

 

Date Posted: 26 July 2017

This document has been peer reviewed.