AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation

Saša Peter, Bastiaan H.A. Urbanus, Remco V. Klaassen, Bin Wu, Henk Jan Boele, Sameha Azizi, Johan A. Slotman, Adriaan B. Houtsmuller, Martijn Schonewille, Freek E. Hoebeek, Sabine Spijker, August B. Smit*, Chris I. De Zeeuw

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The majority of excitatory postsynaptic currents in the brain are gated through AMPA-type glutamate receptors, the kinetics and trafficking of which can be modulated by auxiliary proteins. It remains to be elucidated whether and how auxiliary proteins can modulate synaptic function to contribute to procedural memory formation. In this study, we report that the AMPA-type glutamate receptor (AMPAR) auxiliary protein SHISA6 (CKAMP52) is expressed in cerebellar Purkinje cells, where it co-localizes with GluA2-containing AMPARs. The absence of SHISA6 in Purkinje cells results in severe impairments in the adaptation of the vestibulo-ocular reflex and eyeblink conditioning. The physiological abnormalities include decreased presence of AMPARs in synaptosomes, impaired excitatory transmission, increased deactivation of AMPA receptors, and reduced induction of long-term potentiation at Purkinje cell synapses. Our data indicate that Purkinje cells require SHISA6-dependent modification of AMPAR function in order to facilitate cerebellar, procedural memory formation.

Original languageEnglish
Article number107515
JournalCell Reports
Volume31
Issue number2
DOIs
Publication statusPublished - 14 Apr 2020

Funding

We would like to express our gratitude for excellent technical assistance by Elize Haasdijk, Mandy Rutteman, and Laura Post. Financial support for C.I.D.Z. was provided by the Netherlands Organisation for Scientific Research (NWO-ALW), the Dutch Organization for Medical Sciences (ZonMW), ERC-adv , ERC-POC , EU-LISTEN, Medical NeuroDelta , and INTENSE (NWO-LSH). R.V.K. was funded by NWO-ALW grant ( ALW2PJ/12048 ), S.S. by an NWO VICI grant ( ALW-Vici 016.150.673/865.14.002 ), and M.S. by an ERC-StG grant ( 680235 ).

FundersFunder number
Dutch Organization for Medical Sciences
ERC-PoC
ERC-StG
ERC-adv
EU-LISTEN
INTENSE
Medical NeuroDelta
NWO-ALW
NWO-LSHALW2PJ/12048
Horizon 2020 Framework Programme680235
ZonMw
Nederlandse Organisatie voor Wetenschappelijk OnderzoekALW-Vici 016.150.673/865.14.002

    Keywords

    • AMPAR kinetics
    • auxiliary subunit
    • cerebellum
    • long-term depression
    • procedural memory
    • synapse

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