Gandolfi, Daniela and Cerri, Silvia and Mapelli, Jonathan and Polimeni, Mariarosa and Tritto, Simona and Fuzzati-Armentero, Marie-Therese and Bigiani, Albertino and Blandini, Fabio and Mapelli, Lisa and D’Angelo, Egidio (2017) Activation of the CREB/c-Fos Pathway during Long-Term Synaptic Plasticity in the Cerebellum Granular Layer. Frontiers in Cellular Neuroscience, 11. ISSN 1662-5102
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Abstract
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.
Item Type: | Article |
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Subjects: | Eurolib Press > Medical Science |
Depositing User: | Managing Editor |
Date Deposited: | 07 Jun 2023 04:43 |
Last Modified: | 02 Nov 2023 05:58 |
URI: | http://info.submit4journal.com/id/eprint/2028 |