title: The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner.
abstract: Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signalling regulator, protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster and its selective regulation during memory formation. Inhibiting nuclear PP1 in the mouse brain, or training on an object recognition task similarly increases miR-183/96/182 expression in the hippocampus. Mimicking this increase by miR-183/96/182 overexpression enhances object memory, while knocking-down endogenous miR-183/96/182 impairs it. This effect involves the modulation of several plasticity-related genes, with HDAC9 identified as an important functional target. Further, PP1 controls miR-183/96/182 in a transcription-independent manner through the processing of their precursors. These findings provide novel evidence for a role of miRNAs in memory formation and suggest the implication of PP1 in miRNAs processing in the adult brain.
authors: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich, Zurich CH-8057, Switzerland.
authors: Bisrat T
authors: BT
authors: Woldemichael
authors: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich, Zurich CH-8057, Switzerland.
authors: Ali
authors: A
authors: Jawaid
authors: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich, Zurich CH-8057, Switzerland.
authors: Eloïse A
authors: EA
authors: Kremer
authors: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich, Zurich CH-8057, Switzerland.
authors: Niharika
authors: N
authors: Gaur
authors: Friedrich Miescher Institute for Biomedical Research, Basel CH-4048, Switzerland.
authors: Jacek
authors: J
authors: Krol
authors: Institute of Agricultural Sciences, Swiss Federal Institute of Technology, Zurich CH-8092, Switzerland.
authors: Antonin
authors: A
authors: Marchais
authors: Laboratory of Neuroepigenetics, University of Zurich/Swiss Federal Institute of Technology, Brain Research Institute, Neuroscience Center Zürich, Zurich CH-8057, Switzerland.
authors: Isabelle M
authors: IM
authors: Mansuy
mesh_terms: D000818:Animals; D005106:Exploratory Behavior; D006624:Hippocampus / Q000378:metabolism; D007858:Learning; D057567:Memory, Long-Term; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D005810:Multigene Family; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D013647:Task Performance and Analysis; D015854:Up-Regulation / Q000235:genetics
chemical_list: D035683:MicroRNAs; D054645:Protein Phosphatase 1