Target Cell Type-Dependent Differences in Ca2+ Channel Function Underlie Distinct Release Probabilities at Hippocampal Glutamatergic Terminals

Target Cell Type-Dependent Differences in Ca2+ Channel Function Underlie Distinct Release Probabilities at Hippocampal Glutamatergic Terminals
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DOI:
10.1523/jneurosci.2024-16.2017
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发表时间:
2017-02-15
影响因子:
5.3
通讯作者:
Holderith, Noemi
Holderith, Noemi
中科院分区:
医学1区
文献类型:
--
作者:
Eltes, Timea;Kirizs, Tekla;Holderith, Noemi

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突触前释放概率(P-r)和短期可塑性的靶细胞类型依赖性差异是增加神经元网络计算能力的皮层微电路的有趣特征。在这里,我们测试的假设,不同的电压门控性钙通道密度突触前活动区(AZ)的基础不同的P-r值。大鼠CA 3锥体细胞轴突终末的双光子Ca 2+成像、三重免疫荧光标记和3D电子显微镜(EM)重建显示,与与小清蛋白阳性中间神经元(IN)突触的高Pr终末中的每个AZ区域的Ca 2+流入量比与mGluR 1 α阳性IN突触的低Pr终末中的高1.7-1.9倍。在高P-r AZ中仅表现出1.15倍的Cav2.1和Cav2.2亚基密度。我们的研究结果表明,靶细胞类型特异性调制的电压门控Ca 2+通道功能或不同的亚基组成的功能差异的潜在机制。此外,高P-r突触的特征还在于更高密度的停靠囊泡,这表明这些机制的协同作用是功能差异的基础。
Target cell type-dependent differences in presynaptic release probability (P-r) and short-term plasticity are intriguing features of cortical microcircuits that increase the computational power of neuronal networks. Here, we tested the hypothesis that different voltage-gated Ca2+ channel densities in presynaptic active zones (AZs) underlie different P-r values. Two-photon Ca2+ imaging, triple immunofluorescent labeling, and 3D electron microscopic (EM) reconstruction of rat CA3 pyramidal cell axon terminals revealed similar to 1.7-1.9 times higher Ca2+ inflow per AZ area in high Pr boutons synapsing onto parvalbumin-positive interneurons (INs) than in low P-r boutons synapsing onto mGluR1 alpha-positive INs. EM replica immunogold labeling, however, demonstrated only 1.15 times larger Cav2.1 and Cav2.2 subunit densities in high P-r AZs. Our results indicate target cell type-specific modulation of voltage-gated Ca2+ channel function or different subunit composition as possible mechanisms underlying the functional differences. In addition, high P-r synapses are also characterized by a higher density of docked vesicles, suggesting that a concerted action of these mechanisms underlies the functional differences.