シナプス・グリア動態の可視化

Visualization of Synapse-glia Dynamics

　情報を送る神経と受け取る神経からなるシナプスに，その直近に存在するグリア細胞を付け加えた“Tripartite synapse（三者から成るシナプス）”^1）という言葉が初めて使われて8年が経ち，アストロサイトがシナプス伝達を積極的に修飾していることを支持する非常に多くの知見が集積してきた。しかしながら，それらの多くは電気生理実験から得られたものであり，それに比して形態学的証拠はいまだ非常に少ない。本稿では，アストロサイトとシナプス構造の形態学的解析について，まずさきがけとなった固定標本による解析を簡単に紹介する。そのあと，本稿の主題である，近年相次いで報告された，生きた組織におけるアストロサイトとシナプス構造の可視化技術と，その技術によって可能となった観察およびその結果について紹介したい。

Abstract

　Increasing evidence indicates the importance of neuron-astrocyte interaction in synaptic function.　However, structural evidence is scarce compared to abundant information from electrophysiological studies.　Meticulous studies using serial electron microscopic technique in hippocampal CA1 and cerebellum provided the earliest knowledge about three-dimensional close relationship between synapses and glial processes.　Nevertheless, morphological observation of synapse-glia interaction in live tissues is important to support the idea of astrocytic effects on synaptic transmission.　Recently several methods enabled live imaging of astrocytes as well as dendritic spines in acute slices and tissues cultures.　The techniques to visualize live astrocytes in brain tissues include transgenic mice (GFAP promoter-GFP), sulforhodamine 101 (SR101) application to the surface of neocortex in vivo, ballistic labeling with EGFP plasmid and recombinant viruses (Semliki Forest virus A7 or adenovirus expressing EGFP).　Live astrocytes in brain tissues showed higher motility than neuronal structures in the vicinity of dendrites.　Astrocytes extend or retract their numerous fine processes and change their volume or shape in a complex manner.　Simultaneous observation of filopodia/spines and astrocytes revealed that filopodia/spines often contact with astrocytic processes and that they showed coordinated morphological dynamics in adult and developmental stage, suggesting possible functions of synapse-astrocyte contacts.　Indeed, the local regulation of filopodial stabilization and maturation into spines by astrocytic contacts was reported.　In the next step any astrocytic structural changes around mature synapses correlated with plastic change of synaptic efficacy, such as long-term potentiation, should be investigated.　Structural relationship between axon terminals and astrocytic processes should also be revealed.　Furthermore, in vivo time-lapse imaging of synapse-astrocyte pairs will soon be accomplished, as techniques of in vivo two-photon imaging showed remarkable progress recently.