17 Bertan, Fabio Wischhof, Lena Sosulina, Liudmila Mittag, Manuel Dalügge, Dennis Fornarelli, Alessandra Gardoni, Fabrizio Marcello, Elena Di Luca, Monica Fuhrmann, Martin Remy, Stefan Bano, Daniele Nicotera, Pierluigi AG Nicotera / Bano ; AG Bano AG Remy AG Fuhrmann Cell death and differentiation Cell death and differentiation Macmillan London 1476-5403 10.1038/s41418-020-0584-2 English 3354 - 3373 12 27 Dendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca2+ transients trigger signaling cascades that determine the plastic remodeling of dendritic spines, which modulate learning and memory. Here, we study in mice the role of the intracellular Ca2+ channel Ryanodine Receptor 2 (RyR2) in synaptic plasticity and memory formation. We demonstrate that loss of RyR2 in pyramidal neurons of the hippocampus impairs maintenance and activity-evoked structural plasticity of dendritic spines during memory acquisition. Furthermore, post-developmental deletion of RyR2 causes loss of excitatory synapses, dendritic sparsification, overcompensatory excitability, network hyperactivity and disruption of spatially tuned place cells. Altogether, our data underpin RyR2 as a link between spine remodeling, circuitry dysfunction and memory acquisition, which closely resemble pathological mechanisms observed in neurodegenerative disorders. ISSN 1476-5403 not unique: **3 hits**. ; PUB:(DE-HGF)16, ; 0, ; Animals Dendritic Spines: physiology Female Hippocampus: metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Neuronal Plasticity: physiology Pyramidal Cells: metabolism Ryanodine Receptor Calcium Release Channel: metabolism Synapses: physiology Journal Article 2020 DZNE-2021-00145 2020 pmc:PMC7853040 pmid:32641776 https://pub.dzne.de/record/154291 https://doi.org/10.1038/s41418-020-0584-2