The NR4A orphan nuclear receptors mediate transcription-dependent hippocampal synaptic plasticity

Neurobiol Learn Mem. 2013 Oct:105:151-8. doi: 10.1016/j.nlm.2013.06.020. Epub 2013 Jul 5.

Abstract

Memory consolidation and long-term potentiation require activity-dependent gene transcription, coordinated by an array of transcription factors. Many members of the nuclear receptor superfamily of transcription factors are expressed in the hippocampus immediately after learning, including the Nr4a family of orphan receptors. These activity-dependent transcription factors are critical for hippocampus-dependent contextual fear and object recognition memory, but their role in hippocampal synaptic function is unknown. In this study, we hypothesized that Nr4a transcription factor function is also necessary for hippocampal long-term potentiation. We used a strain of mice expressing a dominant-negative Nr4a transgene. Hippocampal slices from Nr4aDN mutant mice exhibited impairments in transcription-dependent long-term potentiation and were not sensitive to LTP enhancement by the HDAC inhibitor TSA. These results demonstrate that NR4A transcription factor function mediates mechanisms of synaptic plasticity in the hippocampus.

Keywords: HDAC inhibitor; Hippocampus; Long-term potentiation; Nr4a; Nuclear receptors; Synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CA1 Region, Hippocampal / physiology*
  • Female
  • Long-Term Potentiation / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / physiology
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / genetics
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / metabolism*
  • Transcriptional Activation / physiology*

Substances

  • Nuclear Receptor Subfamily 4, Group A, Member 1