Kater Mandy S J, Badia-Soteras Aina, van Weering Jan R T, Smit August B, Verheijen Mark H G
Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Department of Human Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Amsterdam University Medical Center, Vrije Universiteit Medical Center, Amsterdam, Netherlands.
Front Cell Neurosci. 2023 Jan 26;17:1085690. doi: 10.3389/fncel.2023.1085690. eCollection 2023.
Astrocyte-synapse bi-directional communication is required for neuronal development and synaptic plasticity. Astrocytes structurally interact with synapses using their distal processes also known as leaflets or perisynaptic astrocytic processes (PAPs). We recently showed that these PAPs are retracted from hippocampal synapses, and involved in the consolidation of fear memory. However, whether astrocytic synaptic coverage is affected when memory is impaired is unknown.
Here, we describe in detail an electron microscopy method that makes use of a large number of 2D images to investigate structural astrocyte-synapse interaction in paraformaldehyde fixed brain tissue of mice.
We show that fear memory-induced synaptic activation reduces the interaction between the PAPs and the presynapse, but not the postsynapse, accompanied by retraction of the PAP tip from the synaptic cleft. Interestingly, this retraction is absent in the APP/PS1 mouse model of Alzheimer's disease, supporting the concept that alterations in astrocyte-synapse coverage contribute to memory processing.
星形胶质细胞与突触之间的双向通讯对于神经元发育和突触可塑性是必需的。星形胶质细胞通过其远端突起（也称为小叶或突触周围星形胶质细胞突起，PAPs）与突触进行结构上的相互作用。我们最近发现，这些PAPs会从海马突触缩回，并参与恐惧记忆的巩固。然而，当记忆受损时星形胶质细胞对突触的覆盖是否受到影响尚不清楚。
在此，我们详细描述了一种电子显微镜方法，该方法利用大量二维图像来研究小鼠多聚甲醛固定脑组织中星形胶质细胞与突触之间的结构相互作用。
我们发现恐惧记忆诱导的突触激活减少了PAPs与突触前膜之间的相互作用，但不影响与突触后膜的相互作用，同时伴有PAP尖端从突触间隙缩回。有趣的是，在阿尔茨海默病的APP/PS1小鼠模型中不存在这种缩回现象，这支持了星形胶质细胞对突触覆盖的改变有助于记忆处理的观点。
