Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning

Wataru Kakegawa, Akira Katoh, Sakae Narumi, Eriko Miura, Junko Motohashi, Akiyo Takahashi, Kazuhisa Kohda, Yugo Fukazawa, Michisuke Yuzaki, Shinji Matsuda

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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. Video Abstract: Kakegawa et al. show that AMPA receptor endocytosis at parallel fiber-Purkinje cell synapses in the cerebellar flocculus plays a direct role in motor learning in vivo, using a new optogenetic tool, PhotonSABER, which enables the acute inhibition of AMPA receptor endocytosis during LTD.

Original languageEnglish
Pages (from-to)985-998.e6
JournalNeuron
Volume99
Issue number5
DOIs
Publication statusPublished - 2018 Sep 5

Fingerprint

Optogenetics
Neurotransmitter Receptor
AMPA Receptors
Endocytosis
Learning
Synapses
Purkinje Cells
Vestibulo-Ocular Reflex
Neuronal Plasticity
Glutamate Receptors
Lighting
Synaptic Transmission

Keywords

  • AMPA receptor
  • cerebellum
  • endocytosis
  • long-term depression
  • optogenetics
  • Purkinje cell
  • synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kakegawa, W., Katoh, A., Narumi, S., Miura, E., Motohashi, J., Takahashi, A., ... Matsuda, S. (2018). Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning. Neuron, 99(5), 985-998.e6. https://doi.org/10.1016/j.neuron.2018.07.034

Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning. / Kakegawa, Wataru; Katoh, Akira; Narumi, Sakae; Miura, Eriko; Motohashi, Junko; Takahashi, Akiyo; Kohda, Kazuhisa; Fukazawa, Yugo; Yuzaki, Michisuke; Matsuda, Shinji.

In: Neuron, Vol. 99, No. 5, 05.09.2018, p. 985-998.e6.

Research output: Contribution to journalArticle

Kakegawa, W, Katoh, A, Narumi, S, Miura, E, Motohashi, J, Takahashi, A, Kohda, K, Fukazawa, Y, Yuzaki, M & Matsuda, S 2018, 'Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning', Neuron, vol. 99, no. 5, pp. 985-998.e6. https://doi.org/10.1016/j.neuron.2018.07.034
Kakegawa, Wataru ; Katoh, Akira ; Narumi, Sakae ; Miura, Eriko ; Motohashi, Junko ; Takahashi, Akiyo ; Kohda, Kazuhisa ; Fukazawa, Yugo ; Yuzaki, Michisuke ; Matsuda, Shinji. / Optogenetic Control of Synaptic AMPA Receptor Endocytosis Reveals Roles of LTD in Motor Learning. In: Neuron. 2018 ; Vol. 99, No. 5. pp. 985-998.e6.
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