Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2
Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2
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DOI：
10.1016/j.neuron.2007.05.029
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发表时间：
2007-06-21
期刊：
影响因子：
16.2
通讯作者：
Suedhof, Thomas C.
中科院分区：
文献类型：
--
作者：
Chubykin, Alexander A.;Atasoy, Deniz;Suedhof, Thomas C.
神经配素在体外增强突触形成，但令人惊讶的是，体内突触的产生并不需要神经配素。我们现在表明，在培养的神经元中，神经连接素-1过表达增加兴奋性，但不是抑制性，突触反应，并加强突触NMDAR/AMPAR的比例。相反，神经连接素-2过表达增加抑制性，但不是兴奋性，突触反应。因此，在敲除小鼠中缺失神经配蛋白-1选择性地降低NMDAR/AMPAR比率，而缺失神经配蛋白-2选择性地降低抑制性突触反应。引人注目的是，NMDAR或在NMDAR下游发出信号的CaM-激酶11的慢性抑制抑制了神经连接蛋白-1的突触增强活性，而一般突触活性的慢性抑制抑制了神经连接蛋白-2的突触增强活性。两者合计，这些数据表明，神经连接蛋白不建立，但指定和验证，突触通过活动依赖性机制，不同的神经连接蛋白作用于不同类型的突触。这一假说调和了过度表达和敲除表型，并表明神经配素有助于神经回路的使用依赖性形成。
Neuroligins enhance synapse formation in vitro, but surprisingly are not required for the generation of synapses in vivo. We now show that in cultured neurons, neuroligin-1 overexpression increases excitatory, but not inhibitory, synaptic responses, and potentiates synaptic NMDAR/AMPAR ratios. In contrast, neuroligin-2 overexpression increases inhibitory, but not excitatory, synaptic responses. Accordingly, deletion of neuroligin-1 in knockout mice selectively decreases the NMDAR/AMPAR ratio, whereas deletion of neuroligin-2 selectively decreases inhibitory synaptic responses. Strikingly, chronic inhibition of NMDARs or CaM-Kinase 11, which signals downstream of NMDARs, suppresses the synapse-boosting activity of neuroligin-1, whereas chronic inhibition of general synaptic activity suppresses the synapse-boosting activity of neuroligin-2. Taken together, these data indicate that neuroligins do not establish, but specify and validate, synapses via an activity-dependent mechanism, with different neuroligins acting on distinct types of synapses. This hypothesis reconciles the overexpression and knockout phenotypes and suggests that neuroligins contribute to the use-dependent formation of neural circuits.