PhotonSABER: new tool shedding light on endocytosis and learning mechanisms in vivo

Shinji Matsuda,Wataru Kakegawa,Michisuke Yuzaki

doi:10.1080/19420889.2019.1586048

Shinji Matsuda, Wataru Kakegawa + Show 1 more

Open Access

https://doi.org/10.1080/19420889.2019.1586048

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Abstract

ABSTRACTIn the central nervous system, activity-dependent endocytosis of postsynaptic AMPA-type glutamate receptors (AMPA receptors) is thought to mediate long-term depression (LTD), which is a synaptic plasticity model in various neuronal circuits. However, whether and how AMPA receptor endocytosis and LTD at specific synapses are causally linked to learning and memory in vivo remains unclear. Recently, we developed a new optogenetic tool, PhotonSABER, which could control AMPA receptor endocytosis in temporal, spatial, and cell-type-specific manners at activated synapses. Using PhotonSABER, we found that AMPA receptor endocytosis and LTD at synapses between parallel fibers and Purkinje cells in the cerebellum mediate oculomotor learning. We also found that PhotonSABER could inhibit endocytosis of epidermal growth factor receptors in HeLa cells upon light stimulation. These results demonstrate that PhotonSABER is a powerful tool for analyzing the physiological functions of endocytosis in non-neuronal cells, as well as the roles of LTD in various brain regions.

Highlights

In the central nervous system, activity-dependent endocytosis of postsynaptic amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA receptors) is thought to mediate long-term depression (LTD), which is a synaptic plasticity model in various neuronal circuits
LTD occurs at synapses in various brain regions and is thought to serve as the cellular basis of learning and memory [3], whether and how LTD and AMPA receptor endocytosis at specific synapses are causally linked to learning and memory in vivo remains largely unclear
To clarify whether AMPA receptor endocytosis during LTD is directly linked to oculomotor learning, we developed a new tool that can acutely and reversibly control endocytosis at active synapses in a type-specific manner in vivo

Summary

Introduction

In the central nervous system, activity-dependent endocytosis of postsynaptic AMPA-type glutamate receptors (AMPA receptors) is thought to mediate long-term depression (LTD), which is a synaptic plasticity model in various neuronal circuits. To clarify whether AMPA receptor endocytosis during LTD is directly linked to oculomotor learning, we developed a new tool that can acutely and reversibly control endocytosis at active synapses in a type-specific manner in vivo. (a) PhotonSABER de-acidifies the luminal pH of endosomes upon light stimulation.The luminal pH is acidified by the coordinated activities of vacuolar-type H+-adenosine triphosphatase, chloride channels, and Na+/H+ exchangers (NHEs) in early to late endosomes in wild-type neurons.

Results

Conclusion