| Title: |
mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors |
| Authors: |
Notartomaso S.; Nakao H.; Mascio G.; Scarselli P.; Cannella M.; Zappulla C.; Madonna M.; Motolese M.; Gradini R.; Liberatore F.; Zonta M.; Carmignoto G.; Battaglia G.; Bruno V.; Watanabe M.; Aiba A.; Nicoletti F. |
| Source: |
Scientific reports (Nature Publishing Group) 8 (2018). doi:10.1038/s41598-018-31369-7 ; info:cnr-pdr/source/autori:Notartomaso S.; Nakao H.; Mascio G.; Scarselli P.; Cannella M.; Zappulla C.; Madonna M.; Motolese M.; Gradini R.; Liberatore F.; Zonta M.; Carmignoto G.; Battaglia G.; Bruno V.; Watanabe M.; Aiba A.; Nicoletti F./titolo:mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors/doi:10.1038s41598-018-31369-7/rivista:Scientific reports (Nature Publishing Group)/anno:2018/pagina_da:/pagina_a:/intervallo_pagine:/volume:8 |
| Publisher Information: |
Nature Publishing Group, London , Regno Unito |
| Publication Year: |
2018 |
| Collection: |
PUMAlab (ISTI CNR - Consiglio Nazionale delle Ricerche / National Research Council) |
| Subject Terms: |
Receptors; Metabotropic Glutamate | Schizophrenia | mGlu receptor |
| Description: |
In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1? receptors were barely detectable. The developmental decline of mGlu5 receptors coincided with the appearance of mGlu1? receptors in PCs, and both processes were associated with specular changes in CpG methylation in the corresponding gene promoters. It was the mGlu1 receptor that drove the elimination of mGlu5 receptors from PCs, as shown by data obtained with conditional mGlu1? receptor knockout mice and with targeted pharmacological treatments during critical developmental time windows. The suppressing activity of mGlu1 receptors on mGlu5 receptor was maintained in mature PCs, suggesting that expression of mGlu1? and mGlu5 receptors is mutually exclusive in PCs. These findings add complexity to the the finely tuned mechanisms that regulate PC biology during development and in the adult life and lay the groundwork for an in-depth analysis of the role played by mGlu5 receptors in PC maturation. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:cnr-pdr/author/matricola:5372/CARMIGNOTO/PIERGIORGIO; info:cnr-pdr/author/matricola:14964/ZONTA/MICAELA; http://www.cnr.it/prodotto/i/398597; https://publications.cnr.it/doc/398597 |
| DOI: |
10.1038/s41598-018-31369-7 |
| Availability: |
http://www.cnr.it/prodotto/i/398597; https://publications.cnr.it/doc/398597; https://doi.org/10.1038/s41598-018-31369-7; http://www.scopus.com/inward/record.url?eid=2-s2.0-85052900927&partnerID=q2rCbXpz |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.E0530682 |
| Database: |
BASE |