Tsukamoto-Yasui Masako, Sasaki Takuya, Matsumoto Wataru, Hasegawa Ayako, Toyoda Takeshi, Usami Atsushi, Kubota Yuichi, Ochiai Taku, Hori Tomokatsu, Matsuki Norio, Ikegaya Yuji
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
PLoS One. 2007 Nov 28;2(11):e1250. doi: 10.1371/journal.pone.0001250.
The brain is self-writable; as the brain voluntarily adapts itself to a changing environment, the neural circuitry rearranges its functional connectivity by referring to its own activity. How the internal activity modifies synaptic weights is largely unknown, however. Here we report that spontaneous activity causes complex reorganization of synaptic connectivity without any external (or artificial) stimuli. Under physiologically relevant ionic conditions, CA3 pyramidal cells in hippocampal slices displayed spontaneous spikes with bistable slow oscillations of membrane potential, alternating between the so-called UP and DOWN states. The generation of slow oscillations did not require fast synaptic transmission, but their patterns were coordinated by local circuit activity. In the course of generating spontaneous activity, individual neurons acquired bidirectional long-lasting synaptic modification. The spontaneous synaptic plasticity depended on a rise in intracellular calcium concentrations of postsynaptic cells, but not on NMDA receptor activity. The direction and amount of the plasticity varied depending on slow oscillation patterns and synapse locations, and thus, they were diverse in a network. Once this global synaptic refinement occurred, the same neurons now displayed different patterns of spontaneous activity, which in turn exhibited different levels of synaptic plasticity. Thus, active networks continuously update their internal states through ongoing synaptic plasticity. With computational simulations, we suggest that with this slow oscillation-induced plasticity, a recurrent network converges on a more specific state, compared to that with spike timing-dependent plasticity alone.
大脑具有自我书写能力；当大脑主动使自身适应不断变化的环境时，神经回路会根据自身活动重新排列其功能连接。然而，内部活动如何改变突触权重在很大程度上尚不清楚。在此，我们报告自发活动会在没有任何外部（或人工）刺激的情况下导致突触连接的复杂重组。在生理相关的离子条件下，海马切片中的CA3锥体细胞表现出自发尖峰以及膜电位的双稳态慢振荡，在所谓的“上”和“下”状态之间交替。慢振荡的产生不需要快速突触传递，但其模式由局部回路活动协调。在产生自发活动的过程中，单个神经元获得了双向持久的突触修饰。自发突触可塑性取决于突触后细胞内钙浓度的升高，但不依赖于NMDA受体活性。可塑性的方向和程度因慢振荡模式和突触位置而异，因此在网络中是多样的。一旦这种全局突触优化发生，相同的神经元现在会表现出不同的自发活动模式，进而表现出不同水平的突触可塑性。因此，活跃的网络通过持续的突触可塑性不断更新其内部状态。通过计算模拟，我们表明，与仅具有依赖于尖峰时间的可塑性相比，这种由慢振荡诱导的可塑性会使循环网络收敛到一个更特定的状态。
