Protein phosphatase 1-dependent transcriptional programs for long-term memory and plasticity

J. Graff, K. Koshibu, A. Jouvenceau, P. Dutar, I. M. Mansuy
2010 Learning & memory (Cold Spring Harbor, N.Y.)  
Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and phosphatases (PPs) are important players in these mechanisms. Protein serine/threonine phosphatase 1 (PP1), in particular, was recently shown to be important for
more » ... transcription-dependent memory by regulating chromatin remodeling. However, the impact of PP1 on gene transcription in adult neurons remains not fully delineated. Here, we demonstrate that the nuclear pool of PP1 is associated with transcriptional events involving molecular components of signaling cascades acting as positive and negative regulators of memory and brain plasticity. The data show that inhibiting this pool selectively in forebrain neurons improves memory performance, enhances long-term potentiation (LTP), and modulates gene transcription. These findings highlight an important role for PP1 in the regulation of gene transcription in LTM and synaptic plasticity in the adult brain. [Supplemental material is available online at
doi:10.1101/lm.1766510 pmid:20592054 fatcat:g3kp3hvs3rbhdcwcwcsxiy5epy