PMID- 28701927 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201001 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 11 DP - 2017 TI - Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the Cerebellum Granular Layer. PG - 184 LID - 10.3389/fncel.2017.00184 [doi] LID - 184 AB - The induction of long-term potentiation and depression (LTP and LTD) is thought to trigger gene expression and protein synthesis, leading to consolidation of synaptic and neuronal changes. However, while LTP and LTD have been proposed to play important roles for sensori-motor learning in the cerebellum granular layer, their association with these mechanisms remained unclear. Here, we have investigated phosphorylation of the cAMP-responsive element binding protein (CREB) and activation of the immediate early gene c-Fos pathway following the induction of synaptic plasticity by theta-burst stimulation (TBS) in acute cerebellar slices. LTP and LTD were localized using voltage-sensitive dye imaging (VSDi). At two time points following TBS (15 min and 120 min), corresponding to the early and late phases of plasticity, slices were fixed and processed to evaluate CREB phosphorylation (P-CREB) and c-FOS protein levels, as well as Creb and c-Fos mRNA expression. High levels of P-CREB and Creb/c-Fos were detected before those of c-FOS, as expected if CREB phosphorylation triggered gene expression followed by protein synthesis. No differences between control slices and slices stimulated with TBS were observed in the presence of an N-methyl-D-aspartate receptor (NMDAR) antagonist. Interestingly, activation of the CREB/c-Fos system showed a relevant degree of colocalization with long-term synaptic plasticity. These results show that NMDAR-dependent plasticity at the cerebellum input stage bears about transcriptional and post-transcriptional processes potentially contributing to cerebellar learning and memory consolidation. FAU - Gandolfi, Daniela AU - Gandolfi D AD - Neurophysiology Unit, Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy. AD - Brain Connectivity Center, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS)Pavia, Italy. FAU - Cerri, Silvia AU - Cerri S AD - Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS)Pavia, Italy. FAU - Mapelli, Jonathan AU - Mapelli J AD - Neurophysiology Unit, Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy. AD - Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio EmiliaModena, Italy. FAU - Polimeni, Mariarosa AU - Polimeni M AD - Department of Public Health, Experimental and Forensic Medicine, Human Anatomy Unit, University of PaviaPavia Italy. FAU - Tritto, Simona AU - Tritto S AD - Neurophysiology Unit, Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy. FAU - Fuzzati-Armentero, Marie-Therese AU - Fuzzati-Armentero MT AD - Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS)Pavia, Italy. FAU - Bigiani, Albertino AU - Bigiani A AD - Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio EmiliaModena, Italy. FAU - Blandini, Fabio AU - Blandini F AD - Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS)Pavia, Italy. FAU - Mapelli, Lisa AU - Mapelli L AD - Neurophysiology Unit, Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy. AD - Museo Storico Della Fisica e Centro Studi e Ricerche Enrico FermiRome, Italy. FAU - D'Angelo, Egidio AU - D'Angelo E AD - Neurophysiology Unit, Department of Brain and Behavioral Sciences, University of PaviaPavia, Italy. AD - Brain Connectivity Center, Fondazione Istituto Neurologico Nazionale Casimiro Mondino (IRCCS)Pavia, Italy. LA - eng PT - Journal Article DEP - 20170628 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC5487453 OTO - NOTNLM OT - CREB OT - NMDARs OT - cerebellum OT - gene expression OT - long-term plasticity EDAT- 2017/07/14 06:00 MHDA- 2017/07/14 06:01 PMCR- 2017/01/01 CRDT- 2017/07/14 06:00 PHST- 2017/03/16 00:00 [received] PHST- 2017/06/16 00:00 [accepted] PHST- 2017/07/14 06:00 [entrez] PHST- 2017/07/14 06:00 [pubmed] PHST- 2017/07/14 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2017.00184 [doi] PST - epublish SO - Front Cell Neurosci. 2017 Jun 28;11:184. doi: 10.3389/fncel.2017.00184. eCollection 2017.