Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses.

Astrocytic Ca2+ signals are required for the functional integrity of tripartite synapses.
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DOI:
10.1186/1756-6606-6-6
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发表时间:
2013-01-28
期刊:
影响因子:
3.6
通讯作者:
Itohara S
Itohara S
中科院分区:
医学3区
文献类型:
--
作者:
Tanaka M;Shih PY;Gomi H;Yoshida T;Nakai J;Ando R;Furuichi T;Mikoshiba K;Semyanov A;Itohara S

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神经元活动改变星形胶质细胞中的钙离子(Ca 2+)动力学,但这些变化的生理相关性是有争议的。为了进一步研究这个问题,我们产生了一种诱导型转基因小鼠模型,其中肌醇1,4,5-三磷酸吸收剂“IP 3海绵”的表达减弱了星形胶质细胞Ca 2+信号传导。在这些动物中,海马CA 1区的不对称突触的星形胶质细胞覆盖率降低与钙离子活性减弱相关。减少星形胶质细胞的“保护”的突触促进谷氨酸的“溢出”,这是反映在辐射层星形胶质细胞和增强的N-甲基-D-天冬氨酸受体电流在CA 1锥体神经元响应突发刺激的谷氨酸转运体电流延长。这些小鼠还表现出空间参考记忆和远程背景恐惧记忆的行为障碍,其中涉及海马回路。我们的研究结果表明,IP 3介导的星形胶质细胞Ca 2+信号与海马功能性三联突触的形成相关。
Neuronal activity alters calcium ion (Ca2+) dynamics in astrocytes, but the physiologic relevance of these changes is controversial. To examine this issue further, we generated an inducible transgenic mouse model in which the expression of an inositol 1,4,5-trisphosphate absorbent, “IP3 sponge”, attenuates astrocytic Ca2+ signaling. Attenuated Ca2+ activity correlated with reduced astrocytic coverage of asymmetric synapses in the hippocampal CA1 region in these animals. The decreased astrocytic ‘protection’ of the synapses facilitated glutamate ‘spillover’, which was reflected by prolonged glutamate transporter currents in stratum radiatum astrocytes and enhanced N-methyl-D-aspartate receptor currents in CA1 pyramidal neurons in response to burst stimulation. These mice also exhibited behavioral impairments in spatial reference memory and remote contextual fear memory, in which hippocampal circuits are involved. Our findings suggest that IP3-mediated astrocytic Ca2+ signaling correlates with the formation of functional tripartite synapses in the hippocampus.
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