Synaptic integration of transplanted interneuron progenitor cells into native cortical networks
Synaptic integration of transplanted interneuron progenitor cells into native cortical networks
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DOI：
10.1152/jn.00321.2016
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发表时间：
2016-08-01
影响因子：
2.5
通讯作者：
Baraban, Scott C.
中科院分区：
文献类型：
--
作者：
Howard, MacKenzie A.;Baraban, Scott C.
基于神经元间的细胞移植是一种强大的方法，可以改变包括癫痫在内的各种神经系统疾病的网络功能。新的中间神经元是否以亚型特异性的方式整合到天然神经网络中还没有很好的理解，并且基于中间神经元的细胞疗法的治疗机制，包括突触抑制的作用，也存在争议。在这项研究中，我们测试了移植的中间神经元的亚型特异性整合，使用急性皮层脑切片和可视化膜片钳记录来测量兴奋性突触输入，内在特性和抑制性突触输出。将来自胚胎内侧神经节隆起（MGE）的荧光标记祖细胞用于移植。移植后5周，MGE衍生的小清蛋白阳性（PV +）中间神经元接受兴奋性突触输入，表现出成熟的中间神经元放电特性，并与原生锥体细胞进行功能性突触抑制连接，与原生PV +中间神经元的功能性突触抑制连接相当。这些发现表明，MGE衍生的PV +中间神经元在移植后功能上整合到宿主网络内的亚型适当的生理小生境中。
Interneuron-based cell transplantation is a powerful method to modify network function in a variety of neurological disorders, including epilepsy. Whether new interneurons integrate into native neural networks in a subtype-specific manner is not well understood, and the therapeutic mechanisms underlying interneuron-based cell therapy, including the role of synaptic inhibition, are debated. In this study, we tested subtype-specific integration of transplanted interneurons using acute cortical brain slices and visualized patch-clamp recordings to measure excitatory synaptic inputs, intrinsic properties, and inhibitory synaptic outputs. Fluorescently labeled progenitor cells from the embryonic medial ganglionic eminence (MGE) were used for transplantation. At 5 wk after transplantation, MGE-derived parvalbumin-positive (PV +) interneurons received excitatory synaptic inputs, exhibited mature interneuron firing properties, and made functional synaptic inhibitory connections to native pyramidal cells that were comparable to those of native PV + interneurons. These findings demonstrate that MGE-derived PV + interneurons functionally integrate into subtype-appropriate physiological niches within host networks following transplantation.