Synaptic mechanisms of persistent reverberatory activity in neuronal networks
Synaptic mechanisms of persistent reverberatory activity in neuronal networks
复制标题
DOI：
10.1073/pnas.0500717102
复制
发表时间：
2005-07-19
影响因子：
11.1
通讯作者：
Bi, GQ
中科院分区：
文献类型：
--
作者：
Lau, PM;Bi, GQ
对于大脑功能，如工作记忆和运动规划，神经元回路能够在短暂输入后维持持续的活动。理论研究表明，持续的活动可以存在于循环连接的网络中，作为主动混响。然而，这种混响背后的实际细胞过程并没有很好地理解。在这项研究中，我们调查的基本突触机制负责混响活动的小网络在体外大鼠海马神经元。我们发现，对网络中的一个神经元进行短暂刺激，可以以全有或全无的方式唤起持续数秒的反射活动。混响可能是由反复兴奋引起的，因为它被α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体的部分抑制消除（但不是通过阻断NMDA受体）。相反，用荷包牡丹碱阻断抑制性传递增强了混响。此外，双脉冲刺激与脉冲间的间隔为200-400毫秒的触发混响比单脉冲更有效，显然是通过引发更高水平的异步发射器释放。抑制异步释放EGTA-AM取消混响，而提高异步释放锶大大增强混响。最后，操纵钙摄取或释放细胞内的商店也调制混响的水平。因此，经常被忽视的突触传递的异步阶段在网络混响的涌现现象中起着核心作用。
For brain functions such as working memory and motor planning, neuronal circuits are able to sustain persistent activity after transient inputs. Theoretical studies have suggested that persistent activity can exist in recurrently connected networks as active reverberation. However, the actual cellular processes underlying such reverberation are not well understood. In this study, we investigated the basic synaptic mechanisms responsible for reverberatory activity in small networks of rat hippocampal neurons in vitro. We found that brief stimulation of one neuron in a network could evoke, in an all-or-none fashion, reverberatory activity lasting for seconds. The reverberation was likely to arise from recurrent excitation because it was eliminated by partial inhibition of alpha-amino3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors (but not by blockade of NMDA receptors). In contrast, blocking inhibitory transmission with bicuculline enhanced the reverberation. Furthermore, paired-pulse stimuli with interpulse intervals of 200-400 ms were more effective than single pulses in triggering reverberation, apparently by eliciting higher levels of asynchronous transmitter release. Suppressing asynchronous release by EGTA-AM abolished reverberation, whereas elevating asynchronous release by strontium substantially enhanced reverberation. Finally, manipulating calcium uptake into or release from intracellular stores also modulated the level of reverberation. Thus, the oft-overlooked asynchronous phase of synaptic transmission plays a central role in the emergent phenomenon of network reverberation.