Comparison of NMDA and AMPA Channel Expression and Function between Embryonic and Adult Neurons Utilizing Microelectrode Array Systems.
Comparison of NMDA and AMPA Channel Expression and Function between Embryonic and Adult Neurons Utilizing Microelectrode Array Systems.
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DOI：
10.1021/acsbiomaterials.7b00596
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发表时间：
2017-12-11
影响因子：
5.8
通讯作者：
Hickman JJ
中科院分区：
文献类型：
--
作者：
Edwards D;Sommerhage F;Berry B;Nummer H;Raquet M;Clymer B;Stancescu M;Hickman JJ
微电极阵列（MEA）是用于进行电生理实验的创新工具，用于研究来自分离培养物的神经元群体中的电活动和连接性。依赖于来自胚胎组织的神经元是神经元/MEA混合系统的常见限制，并且可能是一般神经科学研究的限制，并且使用成年神经元可以更紧密地模拟完全功能性的体内参数。自发网络活动，同时记录胚胎和成年大鼠神经元培养MEA上长达10周的体外细胞类型之间的突触连接的特征。将培养物暴露于针对NMDA和AMPA通道的突触传递拮抗剂中，这揭示了体外成人和胚胎网络的显着不同的受体谱。此外，胚胎和成人神经元NMDA和AMPA通道亚单位的表达进行了评价超过五周的体外。结果表明，胚胎组织来源的神经元在规定的条件下在体外几周内不表达成熟的突触通道。因此，胚胎对突触拮抗剂的反应与成人组织来源的神经元显着不同。这些结果特别重要，因为大多数关于胚胎海马神经元的研究都不是在培养2 - 4周后开始的。此外，利用MEA代替膜片钳电生理学避免了大规模的劳动密集型研究。这些结果建立了这种独特的混合系统来自成人海马组织与MEA组合的效用，并提供了一个更合适的代表性的体内功能的药物发现。它可用于神经元发育和再生以及神经退行性疾病、创伤性脑损伤和中风的研究。
Microelectrode arrays (MEAs) are innovative tools used to perform electrophysiological experiments for the study of electrical activity and connectivity in populations of neurons from dissociated cultures. Reliance upon neurons derived from embryonic tissue is a common limitation of neuronal/MEA hybrid systems and perhaps of neuroscience research in general, and the use of adult neurons could model fully functional in vivo parameters more closely. Spontaneous network activity was concurrently recorded from both embryonic and adult rat neurons cultured on MEAs for up to 10 weeks in vitro to characterize the synaptic connections between cell types. The cultures were exposed to synaptic transmission antagonists against NMDA and AMPA channels, which revealed significantly different receptor profiles of adult and embryonic networks in vitro. In addition, both embryonic and adult neurons were evaluated for NMDA and AMPA channel subunit expression over five weeks in vitro. The results established that neurons derived from embryonic tissue did not express mature synaptic channels for several weeks in vitro under defined conditions. Consequently, the embryonic response to synaptic antagonists was significantly different than that of neurons derived from adult tissue sources. These results are especially significant because most studies reported with embryonic hippocampal neurons do not begin at two to four weeks in culture. In addition, the utilization of MEAs in lieu of patch-clamp electrophysiology avoided a large-scale, labor-intensive study. These results establish the utility of this unique hybrid system derived from adult hippocampal tissue in combination with MEAs and offer a more appropriate representation of in vivo function for drug discovery. It has application for neuronal development and regeneration as well as for investigations into neurodegenerative disease, traumatic brain injury, and stroke.
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DOI：
10.1523/jneurosci.0203-11.2011
发表时间：
2011-05-04
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li S;Jin M;Koeglsperger T;Shepardson NE;Shankar GM;Selkoe DJ
通讯作者：
Selkoe DJ
影响因子：
--
作者：
Hofmann, F;Bading, H
通讯作者：
Bading, H
影响因子：
6.1
作者：
Gureviciene, I;Ikonen, S;Tanila, H
通讯作者：
Tanila, H
DOI：
10.1073/pnas.211132798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Kim, CH;Chung, HJ;Huganir, RL
通讯作者：
Huganir, RL
DOI：
10.1073/pnas.95.11.6448
发表时间：
1998-05-26
影响因子：
11.1
作者：
Lambert, MP;Barlow, AK;Klein, WL
通讯作者：
Klein, WL