Microglial interactions with synapses are modulated by visual experience.
Microglial interactions with synapses are modulated by visual experience.
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DOI：
10.1371/journal.pbio.1000527
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发表时间：
2010-11-02
期刊：
影响因子：
9.8
通讯作者：
Majewska AK
中科院分区：
文献类型：
--
作者：
Tremblay MÈ;Lowery RL;Majewska AK
小胶质细胞是大脑的免疫细胞，在非病理条件下与附近的突触元件显示出独特的相互作用，这些突触元件对感觉体验的变化敏感。小胶质细胞是大脑的免疫细胞。在没有病理性损伤的情况下，它们的高度能动的突起持续地调查脑实质并短暂地接触突触元件。除了监测，它们在突触中的生理作用尚不清楚。为了深入了解小胶质细胞在突触结构修饰中的可能作用，我们使用免疫细胞化学电子显微镜，连续切片电子显微镜三维重建，双光子体内成像，以表征在正常和改变感觉体验期间，在幼年小鼠的视觉皮层中小胶质细胞与突触的相互作用。在正常的视觉体验中，大多数小胶质细胞过程显示与多个突触相关元件（包括突触裂隙）直接并置。小胶质细胞的过程也明显包围口袋的细胞外空间。在动力学方面，小胶质细胞过程定位于小的和短暂生长的树突棘附近，通常在2 d内丢失。当经验是通过光剥夺和再曝光操纵，小胶质细胞的过程改变了它们的形态，细胞外空间的分布发生变化，显示吞噬结构，并置突触裂缝更频繁，和包膜突触相关的元素更广泛。虽然光剥夺诱导小胶质细胞变得不那么活跃，并改变了他们的偏好定位到附近的一个子集的较大的树突棘，持续萎缩，光再曝光逆转这些行为。总的来说，这些发现揭示了小胶质细胞与突触相互作用的不同方式，这些方式被感觉经验微妙地改变。这些发现表明，小胶质细胞可能积极地促进健康大脑中特定突触子集的经验依赖性修饰或消除。小胶质细胞是脑损伤免疫反应的重要参与者。在病理性损伤的情况下，小胶质细胞迅速被激活并获得释放影响神经元存活以及突触功能和可塑性的各种炎性分子的能力。与身体其他区域的巨噬细胞类似，活化的小胶质细胞可以吞噬或吞噬细胞碎片，并被认为可以消除突触。在没有病理性损伤的情况下，小胶质细胞更加静止，但这些免疫监视者仍然不断地对其周围环境进行采样并接触邻近的细胞和突触。为了进一步探索小胶质细胞在非病理条件下的突触中的作用，我们使用定量电子显微镜和双光子体内成像来表征幼年小鼠视皮层中静止小胶质细胞和突触元件之间的相互作用。我们还研究了一组小鼠中通过防止光暴露所涉及的“活动依赖性”过程。我们发现在视觉体验的改变过程中，小胶质细胞的行为发生了令人惊讶的变化，例如突触元件的吞噬作用增加，以及与结构动态和瞬时突触子集的相互作用。这些观察结果表明，小胶质细胞可能参与突触结构的修饰或消除，因此积极促进健康大脑的学习和记忆。
Microglia, the brain's immune cells, show unique interactions with nearby synaptic elements under non-pathological conditions that are sensitive to changes in sensory experience. Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain. Microglia are important players in immune responses to brain injury. In the event of pathological insults, microglia rapidly become activated and acquire the ability to release various inflammatory molecules that influence neuronal survival as well as synaptic function and plasticity. Similarly to macrophages in other areas of the body, activated microglia can engulf, or phagocytose, cellular debris and are believed to eliminate synapses. In the absence of pathological insult, microglia are more quiescent, but still, these immune surveillants continually sample their surrounding environment and contact neighboring cells and synapses. To further explore the roles of microglia at synapses under non-pathological conditions, we used quantitative electron microscopy and two-photon in vivo imaging to characterize the interactions between quiescent microglia and synaptic elements in the visual cortex of juvenile mice. We also examined the “activity-dependent” processes involved by preventing light exposure in a group of mice. We show surprising changes in microglial behavior during alterations in visual experience, such as increased phagocytosis of synaptic elements and interaction with subsets of structurally dynamic and transient synapses. These observations suggest that microglia may participate in the modification or elimination of synaptic structures, and therefore actively contribute to learning and memory in the healthy brain.
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影响因子：
16.2
作者：
Holtmaat, AJGD;Trachtenberg, JT;Svoboda, K
通讯作者：
Svoboda, K
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
影响因子：
5.3
作者：
Majewska, AK;Newton, JR;Sur, M
通讯作者：
Sur, M
DOI：
10.1016/s0169-328x(98)00040-0
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ito, D;Imai, Y;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
48
作者：
Mank, Marco;Santos, Alexandre Ferrao;Griesbeck, Oliver
通讯作者：
Griesbeck, Oliver