Synapse-specific adaptations to inactivity in hippocampal circuits achieve homeostatic gain control while dampening network reverberation
Synapse-specific adaptations to inactivity in hippocampal circuits achieve homeostatic gain control while dampening network reverberation
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DOI：
10.1016/j.neuron.2008.05.009
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发表时间：
2008-06-26
期刊：
影响因子：
16.2
通讯作者：
Tsien, Richard W.
中科院分区：
文献类型：
--
作者：
Kim, Jimok;Tsien, Richard W.
由神经元活动的慢性变化引起的突触动态平衡，在培养的神经元中得到了很好的研究，但在更多的生理网络中却没有，在那里，不同的突触回路被保留下来。我们在河豚毒素处理的器官型海马区培养的三组兴奋性突触上表征了不活动诱导的适应。对不活动的适应是突触特有的。海马区通过量突触(齿状突触到CA3和CA3到CA1)上调，符合稳态增益控制，以避免神经元放电的极端限制。然而，慢性不活动降低了CA3到CA3突触的mEPSC频率，这些突触是通过药物或手术分离出来的。这种对重复性突触的下调与传统内稳态的预期相反，显然与典型的获得控制相冲突。然而，这些变化导致由CA3金字塔之间的反馈激发产生的反射爆发因不活动而缩短，从而保护网络免受可能的失控激发。因此，突触对突触重量的特定适应不仅有助于控制内环境平衡，而且还抑制了致痫网络的活动。
Synaptic homeostasis, induced by chronic changes in neuronal activity, is well studied in cultured neurons, but not in more physiological networks where distinct synaptic circuits are preserved. We characterized inactivity-induced adaptations at three sets of excitatory synapses in tetrodotoxin-treated organo-typic hippocampal cultures. The adaptation to inactivity was strikingly synapse specific. Hippocampal throughput synapses (dentate-to-CA3 and CA3-to-CA1) were upregulated, conforming to homeostatic gain control in order to avoid extreme limits of neuronal firing. However, chronic inactivity decreased mEPSC frequency at CA3-to-CA3 synapses, which were isolated pharmacologically or surgically. This downregulation of recurrent synapses was opposite to that expected for conventional homeostasis, in apparent conflict with typical gain control. However, such changes contributed to an inactivity-induced shortening of reverberatory bursts generated by feedback excitation among CA3 pyramids, safeguarding the network from possible runaway excitation. Thus, synapse-specific adaptations of synaptic weight not only contributed to homeostatic gain control, but also dampened epileptogenic network activity.