Mechanisms of Sharp Wave Initiation and Ripple Generation
Mechanisms of Sharp Wave Initiation and Ripple Generation
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DOI：
10.1523/jneurosci.0867-14.2014
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发表时间：
2014-08-20
影响因子：
5.3
通讯作者：
Gulyas, Attila I.
中科院分区：
文献类型：
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作者：
Schlingloff, Daniel;Kali, Szabolcs;Gulyas, Attila I.
在记忆形成过程中，海马区尖锐波纹(SWRs)期间神经元活动的重演是必不可少的。为了了解不规则发生的SWR的启动和周期性波纹产生的潜在机制，我们选择性地操作了小鼠海马片中CA3网络的不同组成部分。我们记录了EPSCs和IPSCs，以检查SWR之前神经元活动的建立，并分析后续SWR事件之间的时间间隔分布。我们的结果表明，SWR是通过一种难解机制和随机机制相结合的方式启动的。当在一组自发活跃的锥体细胞中放电时，SWRs就会启动，从而触发经常性CA3网络中逐渐的、指数式的活动。我们发现，这种紧张性兴奋包膜驱动相互连接的小白蛋白阳性篮子细胞，这些细胞开始通过相互抑制而锁相的涟漪频率尖峰。GABA(A)受体介导的同步电流在局部场电位中引起纹波频率振荡的主要成分，并组织锥体细胞的锁相棘波。小白蛋白阳性细胞的光遗传刺激在锥体细胞中诱发了完整的SWR和EPSC序列。即使在兴奋被阻断的情况下，小白蛋白阳性细胞的紧张性驱动也会引发涟漪振荡。相反，小白蛋白阳性细胞的光遗传沉默中断了SWR或抑制了它们的发生。局部药物应用和模拟实验证实，小白蛋白阳性的胞体周围抑制神经元的活动是纹波频率电流和节律产生的必要条件和充分条件。因此，这些中间神经元不仅在伽马振荡期间，而且在不同的构型中，在组织锥体细胞活动方面都是必不可少的。
Replay of neuronal activity during hippocampal sharp wave-ripples (SWRs) is essential in memory formation. To understand the mechanisms underlying the initiation of irregularly occurring SWRs and the generation of periodic ripples, we selectively manipulated different components of the CA3 network in mouse hippocampal slices. We recorded EPSCs and IPSCs to examine the buildup of neuronal activity preceding SWRs and analyzed the distribution of time intervals between subsequent SWR events. Our results suggest that SWRs are initiated through a combined refractory and stochastic mechanism. SWRs initiate when firing in a set of spontaneously active pyramidal cells triggers a gradual, exponential buildup of activity in the recurrent CA3 network. We showed that this tonic excitatory envelope drives reciprocally connected parvalbumin-positive basket cells, which start ripple-frequency spiking that is phase-locked through reciprocal inhibition. The synchronized GABA(A) receptor-mediated currents give rise to a major component of the ripple-frequency oscillation in the local field potential and organize the phase-locked spiking of pyramidal cells. Optogenetic stimulation of parvalbumin-positive cells evoked full SWRs and EPSC sequences in pyramidal cells. Even with excitation blocked, tonic driving of parvalbumin-positive cells evoked ripple oscillations. Conversely, optogenetic silencing of parvalbumin-positive cells interrupted the SWRs or inhibited their occurrence. Local drug applications and modeling experiments confirmed that the activity of parvalbumin-positive perisomatic inhibitory neurons is both necessary and sufficient for ripple-frequency current and rhythm generation. These interneurons are thus essential in organizing pyramidal cell activity not only during gamma oscillation, but, in a different configuration, during SWRs.