title: Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo.
abstract: 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.
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Chunhai
authors.initials: C
authors.lastname: Chen
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.|Department of Neurology, Lanzhou General Hospital, Lanzhou Military Area Command, Lanzhou, Gansu 730050, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: He
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Lianghong
authors.initials: L
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Wang
authors.affiliation: Brain Research Instrument Innovation Center, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Occupational Health, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Brain Research Center, Third Military Medical University, Chongqing 400038, China.|CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000502:physiology* / Q000601:surgery; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D015398:Signal Transduction / Q000502:physiology; D013003:Somatosensory Cortex / Q000502:physiology*
keywords: astrocytes; glial precursor transplantation; sensory response; somatosensory cortex; two-photon Ca2+ imaging