engBertan, FabioWischhof, LenaRemy, StefanBano, DanieleNicotera, PierluigiSosulina, LiudmilaMittag, ManuelDalügge, DennisFornarelli, AlessandraGardoni, FabrizioMarcello, ElenaDi Luca, MonicaFuhrmann, MartinLoss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability.info:eu-repo/classification/ddc/610AnimalsDendritic Spines: physiologyFemaleHippocampus: metabolismMaleMiceMice, Inbred C57BLMice, KnockoutNeuronal Plasticity: physiologyPyramidal Cells: metabolismRyanodine Receptor Calcium Release Channel: metabolismSynapses: physiologyDendritic 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.Cell death and differentiation 27(12), 3354 - 3373 (2020). doi:10.1038/s41418-020-0584-2info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionMacmillan2020info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/154291https://pub.dzne.de/search?p=id:%22DZNE-2021-00145%22Researchersinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41418-020-0584-2info:eu-repo/semantics/altIdentifier/issn/1350-9047info:eu-repo/semantics/altIdentifier/issn/1476-5403info:eu-repo/semantics/altIdentifier/pmid/pmid:32641776