期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2018
卷号：115
期号：31
页码：8025-8030
DOI：10.1073/pnas.1718582115
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Evidence suggests that astrocytes play key roles in structural and functional organization of neuronal circuits. To understand how astrocytes influence the physiopathology of cerebellar circuits, we cultured cells from cerebella of mice that lack the ATM gene. Mutations in ATM are causative of the human cerebellar degenerative disease ataxia-telangiectasia. Cerebellar cultures grown from Atm −/− mice had disrupted network synchronization, atrophied astrocytic arborizations, reduced autophagy levels, and higher numbers of synapses per neuron than wild-type cultures. Chimeric circuitries composed of wild-type astrocytes and Atm −/− neurons were indistinguishable from wild-type cultures. Adult cerebellar characterizations confirmed disrupted astrocyte morphology, increased GABAergic synaptic markers, and reduced autophagy in Atm −/− compared with wild-type mice. These results indicate that astrocytes can impact neuronal circuits at levels ranging from synaptic expression to global dynamics.
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