Heterophilic Type II Cadherins Are Required for High-Magnitude Synaptic Potentiation in the Hippocampus
Heterophilic Type II Cadherins Are Required for High-Magnitude Synaptic Potentiation in the Hippocampus
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DOI：
10.1016/j.neuron.2017.09.009
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发表时间：
2017-09-27
期刊：
影响因子：
16.2
通讯作者：
Williams, Megan E.
中科院分区：
文献类型：
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作者：
Basu, Raunak;Duan, Xin;Williams, Megan E.
海马CA3神经元与CA1神经元在两层形成突触，即东方层（SO）和辐射层（SR）。每一层都有独特的突触特性，但介导这些差异的分子机制尚不清楚。在这里，我们发现SO突触通常比SR突触有更多的蘑菇棘和更高强度的长期增强（LTP）。此外，我们发现这些差异需要II型经典钙粘蛋白、钙粘蛋白-6、-9和-10。虽然钙粘蛋白通常通过跨细胞亲同性相互作用发挥作用，但我们的研究结果表明，突触前钙粘蛋白-9结合突触后钙粘蛋白-6和-10调节蘑菇脊柱密度和SO层的高强度LTP。这些钙粘蛋白的缺失对SR层中通常观察到的低强度LTP没有影响，这表明钙粘蛋白-6、-9和-10是高强度LTP的守门人。因此，II型钙粘蛋白可能独特地促进与学习和记忆相关的突触变化的特异性和强度。
Hippocampal CA3 neurons form synapses with CA1 neurons in two layers, stratum oriens (SO) and stratum radiatum (SR). Each layer develops unique synaptic properties but molecular mechanisms that mediate these differences are unknown. Here, we show that SO synapses normally have significantly more mushroom spines and higher-magnitude long-term potentiation (LTP) than SR synapses. Further, we discovered that these differences require the Type II classic cadherins, cadherins-6, -9, and -10. Though cadherins typically function via trans-cellular homophilic interactions, our results suggest presynaptic cadherin-9 binds postsynaptic cadherins-6 and -10 to regulate mushroom spine density and high-magnitude LTP in the SO layer. Loss of these cadherins has no effect on the lower-magnitude LTP typically observed in the SR layer, demonstrating that cadherins-6, -9, and -10 are gatekeepers for high-magnitude LTP. Thus, Type II cadherins may uniquely contribute to the specificity and strength of synaptic changes associated with learning and memory.