Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability
Activity-Dependent Structural Plasticity of Perisynaptic Astrocytic Domains Promotes Excitatory Synapse Stability
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DOI：
10.1016/j.cub.2014.06.025
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发表时间：
2014-08-04
期刊：
影响因子：
9.2
通讯作者：
Muller, Dominique
中科院分区：
文献类型：
--
作者：
Bernardinelli, Yann;Randall, Jerome;Muller, Dominique
背景资料：中枢神经系统中的兴奋性突触是高度动态的结构，其可以响应于学习和记忆而显示活动依赖性重塑和稳定。突触被称为突触周星形胶质细胞突起（PAP）的星形胶质细胞复杂的过程所包围。PAP是运动结构，显示快速肌动蛋白依赖性运动，其特征是响应神经元活动的Ca2+升高。尽管有争议的影响，在突触可塑性，在星形胶质细胞和PAP形态dynamics.Results的Ca2+事件的作用仍然不清楚：在海马，我们发现，PAP显示广泛的结构可塑性，通过星形胶质细胞代谢型谷氨酸受体和细胞内钙信号的突触活性调节。诱发长时程增强的突触激活引起短暂的PAP运动性增加，导致突触的星形胶质细胞覆盖增强。选择性激活钙信号在个别PAP使用外源性代谢型受体表达和双光子uncaging再现这些效果，增强脊柱稳定性。成年小鼠的躯体感觉皮层的体内成像显示，通过胡须刺激增加的神经元活动类似地提高PAP运动。这在体内PAP运动与脊柱的覆盖率和预测脊柱stability.Conclusions：本研究确定了一种新的突触和星形胶质细胞，突触活动和突触增强调节PAP结构可塑性，这反过来又决定了突触的命运之间的双向相互作用。这种机制可能代表了星形胶质细胞对学习和记忆过程的重要贡献。
Background: Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca2+ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca2+ events in astrocytes and PAP morphological dynamics remain unclear.Results: In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability.Conclusions: This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.