Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention
Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention
复制标题
DOI：
10.1016/j.neuron.2016.09.031
复制
发表时间：
2016-11-23
期刊：
影响因子：
16.2
通讯作者：
Canossa, Marco
中科院分区：
文献类型：
--
作者：
Vignoli, Beatrice;Battistini, Giulia;Canossa, Marco
神经胶质细胞对神经元活化作出反应并释放神经活性分子（称为“胶质递质”），其可影响突触活性并调节可塑性。在这项研究中，我们使用分子遗传学工具，超微结构显微镜和电生理学来评估脑源性神经营养因子（BDNF）在体内皮质胶质传递中的作用。我们发现，神经胶质细胞回收BDNF，以前分泌的神经元作为前神经营养因子后长时程增强（LTP）诱导的电刺激。在BDNF胶质细胞再循环后，我们观察到邻近神经元上紧密的、时间性的、高度局部化的TrkB磷酸化，这是维持LTP所需的过程。星形胶质细胞参与BDNF再循环代表了一种新的机制，通过这种机制，皮质突触可以扩大BDNF的作用，并提供与获取新记忆相关的突触变化。因此，缺乏BDNF神经胶质细胞再循环的小鼠无法识别熟悉的新物体，这表明在记忆巩固过程中对这一过程的生理需求。
Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor (BDNF) on cortical gliotransmission in vivo. We find that glial cells recycle BDNF that was previously secreted by neurons as pro-neurotrophin following long-term potentiation (LTP)-inducing electrical stimulation. Upon BDNF glial recycling, we observed tight, temporal, highly localized TrkB phosphorylation on adjacent neurons, a process required to sustain LTP. Engagement of BDNF recycling by astrocytes represents a novel mechanism by which cortical synapses can expand BDNF action and provide synaptic changes that are relevant for the acquisition of new memories. Accordingly, mice deficient in BDNF glial recycling fail to recognize familiar from novel objects, indicating a physiological requirement for this process in memory consolidation.