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Tatjana Surdin, Bianca Preissing, Lennard Rohr, Michelle Grömmke, Hanna Böke, Maike Barcik, Zohre Azimi, Dirk Jancke, Stefan Herlitze, Melanie Danelle Mark, Ida Siveke

• Neuronal plasticity underlying cerebellar learning behavior is strongly associated with type 1 \(\underline {metabotropic}\) \(\underline {glutamate}\) \(\underline {receptor}\) (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 \(\underline {melanopsin}\) (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 \(\underline {optogenetic}\) activation of OPN4-mGluR1a inducing LTD at the PF-PC synapse \(\textit {in vitro}\). Moreover, we demonstrate that light activation of mGluR1a \(\underline {signaling}\) \(\underline {pathway}\) by OPN4-mGluR1a in PCs leads to an increase in intrinsic activity of PCs \(\textit {in vivo}\) and improved cerebellum driven learning behavior.