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 language | English |
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Article number | 107515 |
Journal | Cell Reports |
Volume | 31 |
Issue number | 2 |
DOIs | |
Publication status | Published - 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 ).
Funders | Funder number |
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Dutch Organization for Medical Sciences | |
ERC-PoC | |
ERC-StG | |
ERC-adv | |
EU-LISTEN | |
INTENSE | |
Medical NeuroDelta | |
NWO-ALW | |
NWO-LSH | ALW2PJ/12048 |
Horizon 2020 Framework Programme | 680235 |
ZonMw | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | ALW-Vici 016.150.673/865.14.002 |
Keywords
- AMPAR kinetics
- auxiliary subunit
- cerebellum
- long-term depression
- procedural memory
- synapse