Haber Michael, Zhou Lei, Murai Keith K
Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, H3G 1A4, Canada.
J Neurosci. 2006 Aug 30;26(35):8881-91. doi: 10.1523/JNEUROSCI.1302-06.2006.
Accumulating evidence is redefining the importance of neuron-glial interactions at synapses in the CNS. Astrocytes form "tripartite" complexes with presynaptic and postsynaptic structures and regulate synaptic transmission and plasticity. Despite our understanding of the importance of neuron-glial relationships in physiological contexts, little is known about the structural interplay between astrocytes and synapses. In the past, this has been difficult to explore because studies have been hampered by the lack of a system that preserves complex neuron-glial relationships observed in the brain. Here we present a system that can be used to characterize the intricate relationship between astrocytic processes and synaptic structures in situ using organotypic hippocampal slices, a preparation that retains the three-dimensional architecture of astrocyte-synapse interactions. Using time-lapse confocal imaging, we demonstrate that astrocytes can rapidly extend and retract fine processes to engage and disengage from motile postsynaptic dendritic spines. Surprisingly, astrocytic motility is, on average, higher than its dendritic spine counterparts and likely relies on actin-based cytoskeletal reorganization. Changes in astrocytic processes are typically coordinated with changes in spines, and astrocyte-spine interactions are stabilized at larger spines. Our results suggest that dynamic structural changes in astrocytes help control the degree of neuron-glial communication at hippocampal synapses.
越来越多的证据正在重新定义中枢神经系统(CNS)突触处神经元与神经胶质细胞相互作用的重要性。星形胶质细胞与突触前和突触后结构形成“三方”复合体,并调节突触传递和可塑性。尽管我们了解神经元与神经胶质细胞关系在生理环境中的重要性,但对于星形胶质细胞与突触之间的结构相互作用却知之甚少。过去,这很难进行探究,因为研究受到缺乏一个能保留大脑中观察到的复杂神经元与神经胶质细胞关系的系统的阻碍。在这里,我们展示了一个系统,该系统可用于利用器官型海马切片原位表征星形胶质细胞突起与突触结构之间的复杂关系,这种制备方法保留了星形胶质细胞与突触相互作用的三维结构。通过延时共聚焦成像,我们证明星形胶质细胞可以快速伸展和缩回精细突起,以与运动性突触后树突棘接触和脱离。令人惊讶的是,星形胶质细胞的运动性平均高于其树突棘对应物,并且可能依赖于基于肌动蛋白的细胞骨架重组。星形胶质细胞突起的变化通常与棘突的变化相协调,并且星形胶质细胞与棘突的相互作用在较大的棘突处稳定下来。我们的结果表明,星形胶质细胞的动态结构变化有助于控制海马突触处神经元与神经胶质细胞的通讯程度。