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

2016; eLife Sciences Publications Ltd; Volume: 5; Linguagem: Inglês

10.7554/elife.17361

2050-084X

Clemens Jaitner, Chethan Reddy, Andreas Abentung, Nigel Whittle, Dietmar Rieder, Andrea Delekate, Martin Körte, Gaurav Jain, André Fischer, Farahnaz Sananbenesi, Isabella Cera, Nicolas Singewald, Georg Dechant, Galina Apostolova,

MicroRNA in disease regulation

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.