Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning

Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning
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DOI:
10.1126/science.1151120
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发表时间:
2008-02-29
期刊:
影响因子:
56.9
通讯作者:
Tonegawa, Susumu
Tonegawa, Susumu
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Nakashiba, Toshiaki;Young, Jennie Z.;Tonegawa, Susumu

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海马体是大脑中涉及学习和记忆的一个区域。它包含被称为三突触通路(其信息传递如下:内嗅皮层→齿状回→CA3→CA1→内嗅皮层)和单突触通路(内嗅皮层→CA1→内嗅皮层)的平行兴奋性通路。我们为转基因小鼠开发了一种普遍适用的基于破伤风毒素的方法,该方法允许对突触传递进行诱导性和可逆性抑制,并将其应用于三突触通路,同时保留单突触通路的传递。我们发现三突触通路中CA3的突触输出是可有可无的,而短的单突触通路对于渐进式空间学习是足够的。相比之下,包含CA3的完整三突触通路对于快速的一次性情境学习、基于模式完成的记忆回忆以及CA1细胞的空间调谐是必需的。
The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway ( which carries information as follows: entorhinal cortex --> dentate gyrus --> CA3 --> CA1 --> entorhinal cortex) and the monosynaptic pathway ( entorhinal cortex --> CA1 --> entorhinal cortex). We developed a generally applicable tetanus toxin - based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid one- trial contextual learning, for pattern completion based memory recall, and for spatial tuning of CA1 cells.