TY  - JOUR
AU  - Bertan, Fabio
AU  - Wischhof, Lena
AU  - Sosulina, Liudmila
AU  - Mittag, Manuel
AU  - Dalügge, Dennis
AU  - Fornarelli, Alessandra
AU  - Gardoni, Fabrizio
AU  - Marcello, Elena
AU  - Di Luca, Monica
AU  - Fuhrmann, Martin
AU  - Remy, Stefan
AU  - Bano, Daniele
AU  - Nicotera, Pierluigi
TI  - Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability.
JO  - Cell death and differentiation
VL  - 27
IS  - 12
SN  - 1476-5403
CY  - London
PB  - Macmillan
M1  - DZNE-2021-00145
SP  - 3354 - 3373
PY  - 2020
N1  - ISSN 1476-5403 not unique: **3 hits**.
AB  - 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.
KW  - Animals
KW  - Dendritic Spines: physiology
KW  - Female
KW  - Hippocampus: metabolism
KW  - Male
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Mice, Knockout
KW  - Neuronal Plasticity: physiology
KW  - Pyramidal Cells: metabolism
KW  - Ryanodine Receptor Calcium Release Channel: metabolism
KW  - Synapses: physiology
LB  - PUB:(DE-HGF)16
C6  - pmid:32641776
C2  - pmc:PMC7853040
DO  - DOI:10.1038/s41418-020-0584-2
UR  - https://pub.dzne.de/record/154291
ER  -