Activity- and BDNF-induced plasticity of miniature synaptic currents in ES cell-derived neurons integrated in a neocortical network
Activity- and BDNF-induced plasticity of miniature synaptic currents in ES cell-derived neurons integrated in a neocortical network
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DOI：
10.1152/jn.00155.2005
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发表时间：
2005-12-01
影响因子：
2.5
通讯作者：
Gottmann, K
中科院分区：
文献类型：
--
作者：
Copi, A;Jüngling, K;Gottmann, K
科比、安德里亚、凯永玲和库尔特·戈特曼。在整合到新皮质网络中的ES细胞来源的神经元中，活动和BDNF诱导的微小突触电流的可塑性。《神经生理学杂志》94：4538-4543,2005；DOI：10.1152/jn.00155.2005。体外分化的胚胎干细胞被认为是神经退行性疾病细胞替代治疗的潜在供体细胞。这类细胞的功能性突触整合似乎是可以想象的，因为众所周知，ES细胞来源的神经元建立兴奋性和抑制性突触。然而，在这些突触中，记忆形成的先决条件--长期突触可塑性尚未被证明。在体外分化和免疫分离纯化后，我们将ES细胞来源的神经元与新皮质组织块共培养，强烈地神经支配了ES细胞来源的靶神经元。ES细胞来源的神经元表现出与原代培养的新皮质神经元相似的动作电位放电。由AMPA受体介导的微小兴奋性突触后电流(AMPA MEPSCs)指示谷氨酸能突触的形成。此外，还观察到了N-甲基-D-天冬氨酸受体介导的D-2-氨基-5-膦戊酸敏感的mEPSC成分。我们首先研究了谷氨酸能突触的mEPSCs的活性依赖的稳态可塑性(突触伸缩)。TTX慢性阻断动作电位活动导致AMPA mEPSCs波幅增加。这表明ES细胞来源的神经元能够对突触后AMPA受体进行动态平衡调节。此外，我们还研究了神经营养素对谷氨酸能突触mEPSCs的突触可塑性。在培养液中长期加入脑源性神经营养因子(BDNF；100 ng/ml)，AMPA mEPSCs的频率和幅度均增加。这些结果表明，BDNF诱导突触前释放部位的形成和/或功能成熟与突触后AMPA受体的上调是平行的。因此，BDNF是一种潜在的辅助因子，可以促进ES细胞来源的神经元与新皮质网络的功能性突触整合。
Copi, Andrea, Kay Jungling, and Kurt Gottmann. Activity- and BDNF- induced plasticity of miniature synaptic currents in EScellderived neurons integrated in a neocortical network. J Neurophysiol 94:4538-4543,2005;doi:10.1152/jn.00155.2005. In vitro differentiated embryonic stem (ES) cells have been proposed as potential donor cells for cell replacement therapies of neurodegenerative diseases. The functional synaptic integration of such cells appears conceivable because ES cell-derived neurons are well known to establish excitatory and inhibitory synapses. However, long-term synaptic plasticity, a prerequisite of memory formation, has not yet been demonstrated at these synapses. After in vitro differentiation and purification by immunoisolation, we co-cultured ES cell-derived neurons with neocortical explants, which strongly innervated the ES cell- derived target neurons. ES cell- derived neurons exhibited action potential firing similar to primary cultured neocortical neurons. The formation of glutamatergic synapses was indicated by AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA mEPSCs). In addition, a N-methyl-D-aspartate receptor-mediated, D-2-amino-5-phosphonopentanoic acid-sensitive mEPSC component was observed. We first studied activity-dependent homeostatic plasticity (synaptic scaling) of mEPSCs at glutamatergic synapses. Chronic blockade of action potential activity by TTX resulted in an increase in the amplitudes of AMPA mEPSCs. This indicates that ES cell- derived neurons are capable of a homeostatic regulation of postsynaptic AMPA receptors. In addition, we investigated neurotrophin-induced synaptic plasticity of mEPSCs at glutamatergic synapses. Chronic addition of brain-derived neurotrophic factor (BDNF; 100 ng/ml) to the culture medium resulted in an increase in both the frequency and the amplitudes of AMPA mEPSCs. These results suggest that BDNF induces the formation and/or the functional maturation of presynaptic release sites in parallel with an upregulation of postsynaptic AMPA receptors. Thus BDNF represents a potential co-factor that could improve functional synaptic integration of ES cell- derived neurons into neocortical networks.