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000154291 0247_ $$2doi$$a10.1038/s41418-020-0584-2
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000154291 037__ $$aDZNE-2021-00145
000154291 041__ $$aEnglish
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000154291 1001_ $$0P:(DE-2719)2810664$$aBertan, Fabio$$b0$$eFirst author$$udzne
000154291 245__ $$aLoss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability.
000154291 260__ $$aLondon$$bMacmillan$$c2020
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000154291 520__ $$aDendritic 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.
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000154291 650_2 $$2MeSH$$aAnimals
000154291 650_2 $$2MeSH$$aDendritic Spines: physiology
000154291 650_2 $$2MeSH$$aFemale
000154291 650_2 $$2MeSH$$aHippocampus: metabolism
000154291 650_2 $$2MeSH$$aMale
000154291 650_2 $$2MeSH$$aMice
000154291 650_2 $$2MeSH$$aMice, Inbred C57BL
000154291 650_2 $$2MeSH$$aMice, Knockout
000154291 650_2 $$2MeSH$$aNeuronal Plasticity: physiology
000154291 650_2 $$2MeSH$$aPyramidal Cells: metabolism
000154291 650_2 $$2MeSH$$aRyanodine Receptor Calcium Release Channel: metabolism
000154291 650_2 $$2MeSH$$aSynapses: physiology
000154291 7001_ $$0P:(DE-2719)2811527$$aWischhof, Lena$$b1$$udzne
000154291 7001_ $$0P:(DE-2719)2810715$$aSosulina, Liudmila$$b2$$udzne
000154291 7001_ $$0P:(DE-2719)2811044$$aMittag, Manuel$$b3$$udzne
000154291 7001_ $$0P:(DE-2719)2811426$$aDalügge, Dennis$$b4$$udzne
000154291 7001_ $$0P:(DE-2719)2690858$$aFornarelli, Alessandra$$b5$$udzne
000154291 7001_ $$0P:(DE-HGF)0$$aGardoni, Fabrizio$$b6
000154291 7001_ $$0P:(DE-HGF)0$$aMarcello, Elena$$b7
000154291 7001_ $$0P:(DE-HGF)0$$aDi Luca, Monica$$b8
000154291 7001_ $$0P:(DE-2719)2679991$$aFuhrmann, Martin$$b9$$udzne
000154291 7001_ $$0P:(DE-2719)2810375$$aRemy, Stefan$$b10$$udzne
000154291 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b11$$eCorresponding author$$udzne
000154291 7001_ $$0P:(DE-2719)2010732$$aNicotera, Pierluigi$$b12$$eLast author$$udzne
000154291 773__ $$0PERI:(DE-600)1496681-5$$a10.1038/s41418-020-0584-2$$gVol. 27, no. 12, p. 3354 - 3373$$n12$$p3354 - 3373$$tCell death and differentiation$$v27$$x1476-5403$$y2020
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