Department of Zoology and Neurobiology, Ruhr-University Bochum, Bochum, Germany
Maike Barcik
Cardiovascular Research Institute Düsseldorf, Division of Cardiology, Pulmonology, and Vascular Medicine, University Duesseldorf, Medical Faculty, Duesseldorf, Germany
Zohre Azimi
Optical Imaging Group, Institut für Neuroinformatik, Ruhr-University Bochum, Bochum, Germany
Dirk Jancke
Optical Imaging Group, Institut für Neuroinformatik, Ruhr-University Bochum, Bochum, Germany
Stefan Herlitze
Department of Zoology and Neurobiology, Ruhr-University Bochum, Bochum, Germany; Corresponding author
Department of Zoology and Neurobiology, Ruhr-University Bochum, Bochum, Germany; Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany; Corresponding author
Summary: 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 Gq/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 Gq/11 pathway to the C-termini of mGluR1 splice variants (OPN4-mGluR1a and OPN4-mGluR1b). Activation of both OPN4-mGluR1 variants showed robust Ca2+ 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.
