Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning
Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning
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DOI：
10.1016/j.neuron.2018.07.034
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发表时间：
2018-09-05
期刊：
影响因子：
16.2
通讯作者：
Matsuda, Shinji
中科院分区：
文献类型：
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作者：
Kakegawa, Wataru;Katoh, Akira;Matsuda, Shinji
AMPA型谷氨酸受体（AMPA受体）介导的突触传递的长期抑制（LTD）已被认为是学习和记忆的细胞底物。虽然活动诱导的AMPA受体内吞作用被认为是LTD的基础，但在很大程度上仍不清楚LTD和特定突触处的AMPA受体内吞作用是否与体内学习和记忆有因果关系。在这里，我们开发了一种新的光遗传学工具，称为PhotonSABER，它能够在活跃的突触上对AMPA受体内吞作用进行时间、空间和细胞类型特异性控制，而基础突触特性和其他形式的突触可塑性不受影响。我们发现，纤维照明浦肯野细胞表达PhotonSABER在体内抑制小脑运动学习的适应过程中的水平视动反应和前庭眼反射，以及突触AMPA受体减少的绒球。我们的研究结果表明，LTD和AMPA受体在特定的神经回路的内吞作用是直接负责在体内的运动学习。
Long-term depression (LTD) of AMPA-type glutamate receptor (AMPA receptor)-mediated synaptic transmission has been proposed as a cellular substrate for learning and memory. Although activity-induced AMPA receptor endocytosis is believed to underlie LTD, it remains largely unclear whether LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo. Here we developed a new optogenetic tool, termed PhotonSABER, which enabled the temporal, spatial, and cell-type-specific control of AMPA receptor endocytosis at active synapses, while the basal synaptic properties and other forms of synaptic plasticity were unaffected. We found that fiberoptic illumination to Purkinje cells expressing PhotonSABER in vivo inhibited cerebellar motor learning during adaptation of the horizontal optokinetic response and vestibulo-ocular reflex, as well as synaptic AMPA receptor decrease in the flocculus. Our results demonstrate that LTD and AMPA receptor endocytosis at specific neuronal circuits were directly responsible for motor learning in vivo.