Artificial association of memory events by optogenetic stimulation of hippocampal CA3 cell ensembles
Artificial association of memory events by optogenetic stimulation of hippocampal CA3 cell ensembles
复制标题
DOI：
10.1186/s13041-018-0424-1
复制
发表时间：
2019-01-08
期刊：
影响因子：
3.6
通讯作者：
Inokuchi, Kaoru
中科院分区：
文献类型：
--
作者：
Oishi, Naoya;Nomoto, Masanori;Inokuchi, Kaoru
先前使用光遗传学技术的功能获得研究表明，海马齿状回或CA 1细胞系综的操纵对于记忆再激活和产生合成或虚假记忆是重要的。然而，操纵CA 3细胞系综的功能获得性研究尚未报道。海马体的CA 3区包括一个循环兴奋回路，其被认为对于在一个大脑区域内存储的信息之间产生关联是重要的。我们研究了是否在一个大脑区域，海马CA 3区的细胞群的一致发射，关联不同的事件。用通道视紫红质-2（ChR 2）-mCherry标记对背景探索和背景恐惧条件反射作出反应的CA 3细胞系。这些集合的同步激活在中性环境中诱导小鼠的冻结行为，其中从未传递过足部电击。这种人工联想恐惧记忆的回忆是特定于环境的。在体内电生理记录表明，20 Hz的光学刺激的ChR 2-mCherry表达的CA 3神经元，这是在行为实验中使用的相同的刺激协议，诱导长时程增强在CA 3-CA 3突触。总之，这些结果表明，在一个大脑区域，海马CA 3区的合奏的同步激活，是足够的不同的事件的关联。我们的电生理学结果潜在地表明，这种记忆事件的人工关联可能是通过循环回路加强CA 3系综之间的突触效能而诱导的。
Previous gain-of-function studies using an optogenetic technique showed that manipulation of the hippocampal dentate gyrus or CA1 cell ensembles is important for memory reactivation and to generate synthetic or false memory. However, gain-of-function study manipulating CA3 cell ensembles has not been reported. The CA3 area of the hippocampus comprises a recurrent excitatory circuit, which is thought to be important for the generation of associations among the stored information within one brain region. We investigated whether the coincident firing of cell ensembles in one brain region, hippocampal CA3, associates distinct events. CA3 cell ensembles responding to context exploration and during contextual fear conditioning were labeled with channelrhodopsin-2 (ChR2)-mCherry. The synchronous activation of these ensembles induced freezing behavior in mice in a neutral context, in which a foot shock had never been delivered. The recall of this artificial associative fear memory was context specific. In vivo electrophysiological recordings showed that 20-Hz optical stimulation of ChR2-mCherry-expressing CA3 neurons, which is the same stimulation protocol used in behavioral experiment, induced long-term potentiation at CA3-CA3 synapses. Altogether, these results demonstrate that the synchronous activation of ensembles in one brain region, CA3 of the hippocampus, is sufficient for the association of distinct events. The results of our electrophysiology potentially suggest that this artificial association of memory events might be induced by the strengthening of synaptic efficacy between CA3 ensembles via recurrent circuit.