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Publication : Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity.

First Author  Surdin T Year  2023
Journal  iScience Volume  26
Issue  1 Pages  105828
PubMed ID  36632066 Mgi Jnum  J:332553
Mgi Id  MGI:7427127 Doi  10.1016/j.isci.2022.105828
Citation  Surdin T, et al. (2023) Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity. iScience 26(1):105828
abstractText  Neuronal plasticity underlying cerebellar learning behavior is strongly associated with type 1 metabotropic glutamate receptor (mGluR1) signaling. Activation of mGluR1 leads to activation of the G(q/11) pathway, which is involved in inducing synaptic plasticity at the parallel fiber-Purkinje cell synapse (PF-PC) in form of long-term depression (LTD). To optogenetically modulate mGluR1 signaling we fused mouse melanopsin (OPN4) that activates the G(q/11) pathway to the C-termini of mGluR1 splice variants (OPN4-mGluR1a and OPN4-mGluR1b). Activation of both OPN4-mGluR1 variants showed robust Ca(2+) increase in HEK cells and PCs of cerebellar slices. We provide the prove-of-concept approach to modulate synaptic plasticity via optogenetic activation of OPN4-mGluR1a inducing LTD at the PF-PC synapse in vitro. Moreover, we demonstrate that light activation of mGluR1a signaling pathway by OPN4-mGluR1a in PCs leads to an increase in intrinsic activity of PCs in vivo and improved cerebellum driven learning behavior.
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