Format

Send to

Choose Destination
Elife. 2016 Nov 29;5. pii: e17361. doi: 10.7554/eLife.17361.

Satb2 determines miRNA expression and long-term memory in the adult central nervous system.

Author information

1
Institute for Neuroscience, Medical University of Innsbruck, Innsbruck, Austria.
2
Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria.
3
Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
4
Zoological Institute, Technical University Braunschweig, Braunschweig, Germany.
5
AG Neuroinflammation and Neurodegeneration (NIND), Braunschweig, Germany.
6
Research Group for Epigenetics in Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Göttingen, Germany.
7
Research Group for Complex Neurodegenerative Disorders, German Center for Neurodegenerative Diseases, Göttingen, Germany.
8
Department of Psychiatry and Psychotherapy, University Medical Center, German Center for Neurodegenerative Diseases, Göttingen, Germany.

Abstract

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

KEYWORDS:

LTP; chromatin; chromosomes; genes; long-term memory; miRNA; mouse; neuroscience; synaptic plasticity

PMID:
27897969
PMCID:
PMC5207769
DOI:
10.7554/eLife.17361
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center