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Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundam...

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Detalles Bibliográficos
Autores principales: Zhang, Kuan, Chen, Chunhai, Yang, Zhiqi, He, Wenjing, Liao, Xiang, Ma, Qinlong, Deng, Ping, Lu, Jian, Li, Jingcheng, Wang, Meng, Li, Mingli, Zheng, Lianghong, Zhou, Zhuan, Sun, Wei, Wang, Liting, Jia, Hongbo, Yu, Zhengping, Zhou, Zhou, Chen, Xiaowei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004757/
https://www.ncbi.nlm.nih.gov/pubmed/27405333
http://dx.doi.org/10.1093/cercor/bhw213
Descripción
Sumario:Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca(2+) imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca(2+) signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo.