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

Shinji Matsuda; Wataru Kakegawa; Michisuke Yuzaki

doi:10.1080/19420889.2019.1586048

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

Commun Integr Biol. 2019 Mar 16;12(1):34-37. doi: 10.1080/19420889.2019.1586048. eCollection 2019.

Authors

Shinji Matsuda^{1

2

3}, Wataru Kakegawa¹, Michisuke Yuzaki¹

Affiliations

¹ Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
² Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, Tokyo, Japan.
³ Brain Science Inspired Life Support Research Center (BLSC), The University of Electro-Communications, Tokyo, Japan.

Abstract

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. 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.

Keywords: AMPA receptor; Long-term depression; Purkinje cell; optogenetics; synapse.

Grants and funding

This work was supported by the JST-PRESTO [11102645 to S.M.], the JST-CREST [JPMJCR1854, M.Y.]; MEXT/JSPS KAKENHI Grants [16H06461, 15H05772 to M.Y.; 18H04563, 17H05579, 17H04020 to W.K.; and 17K07048 to S.M.]; the AMED [16dm0107124h0001 to W.K.], and the Takeda Science Foundation (W.K.).