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兰尼碱受体2的缺失会损害神经元活动依赖的树突棘重塑，并引发代偿性神经元过度兴奋。

Loss of Ryanodine Receptor 2 impairs neuronal activity-dependent remodeling of dendritic spines and triggers compensatory neuronal hyperexcitability.

作者信息

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

机构信息

German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.

出版信息

Cell Death Differ. 2020 Dec;27(12):3354-3373. doi: 10.1038/s41418-020-0584-2. Epub 2020 Jul 8.

DOI:10.1038/s41418-020-0584-2
PMID:32641776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7853040/
Abstract

Dendritic spines are postsynaptic domains that shape structural and functional properties of neurons. Upon neuronal activity, Ca 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 Ca 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.

摘要

树突棘是塑造神经元结构和功能特性的突触后结构域。在神经元活动时，钙瞬变触发信号级联反应，决定树突棘的可塑性重塑，而树突棘的可塑性重塑可调节学习和记忆。在此，我们在小鼠中研究细胞内钙通道兰尼碱受体2（RyR2）在突触可塑性和记忆形成中的作用。我们证明，海马锥体神经元中RyR2的缺失会损害记忆获取过程中树突棘的维持以及活动诱发的结构可塑性。此外，发育后RyR2的缺失会导致兴奋性突触丧失、树突稀疏、过度代偿性兴奋性、网络活动亢进以及空间调谐位置细胞的破坏。总之，我们的数据支持RyR2是脊柱重塑、电路功能障碍和记忆获取之间的联系，这与神经退行性疾病中观察到的病理机制非常相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/dbae529ef04d/41418_2020_584_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/9ff7dda20a96/41418_2020_584_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/8bb92212d11d/41418_2020_584_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/5e149c7e39e4/41418_2020_584_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/dbae529ef04d/41418_2020_584_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/9ff7dda20a96/41418_2020_584_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/8bb92212d11d/41418_2020_584_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/5e149c7e39e4/41418_2020_584_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c2/7853040/dbae529ef04d/41418_2020_584_Fig4_HTML.jpg

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