The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory
- Vrije Universiteit, Netherlands
Abstract
Glutamatergic synapses rely on AMPA receptors (AMPARs) for fast synaptic transmission and plasticity. AMPAR auxiliary proteins regulate receptor trafficking, and modulate receptor mobility and its biophysical properties. The AMPAR auxiliary protein Shisa7 (CKAMP59) has been shown to interact with AMPARs in artificial expression systems, but it is unknown whether Shisa7 has a functional role in glutamatergic synapses. We show that Shisa7 physically interacts with synaptic AMPARs in mouse hippocampus. Shisa7 gene deletion resulted in faster AMPAR currents in CA1 synapses, without affecting its synaptic expression. Shisa7 KO mice showed reduced initiation and maintenance of long-term potentiation of glutamatergic synapses. In line with this, Shisa7 KO mice showed a specific deficit in contextual fear memory, both short-term and long-term after conditioning, whereas auditory fear memory and anxiety-related behavior were normal. Thus, Shisa7 is a bona-fide AMPAR modulatory protein affecting channel kinetics of AMPARs, necessary for synaptic hippocampal plasticity, and memory recall.
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Author details
Funding
HEALTH-2009-2.1.2.1 EU-FP7 SynSys (SynSys)
- Marta Ruiperez-Alonso
- Jasper Stroeder
- Huib D Mansvelder
- August B Smit
- Sabine Spijker
Erasmus Mundus (159302-1-2009-1-NL-ERA MUNDUS-EMJD)
- Azra Elia Zamri
NWO-ALW #822.02.020 (#822.02.020)
- Remco V Klaassen
NBSIK PharmaPhenomics FES0908 (FES0908)
- Leanne J M Schmitz
- Rolinka J van der Loo
- August B Smit
NBSIK Mouse Phenomics Consortium BSIK03053 (BSIK03053)
- Priyanka Rao-Ruiz
- Rolinka J van der Loo
- August B Smit
MEST-CT-2005-020919 Neuromics (20919)
- Priyanka Rao-Ruiz
MEST-ITN-2008-238686 CerebNet (238686)
- Jasper Stroeder
NWO-ALW Vici 865.13.002 (865.13.002)
- Huib D Mansvelder
ERC BrainSignals 281443 (281443)
- Huib D Mansvelder
NWO-ALW Vici 016.150.673 / 865.14.002 (016.150.673 / 865.14.002)
- Leanne J M Schmitz
- Sabine Spijker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were performed in accordance to Dutch law and licensing agreements using a protocol approved by the Animal Ethics Committee of the VU University Amsterdam.
Copyright
© 2017, Schmitz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The AMPA receptor-associated protein Shisa7 regulates hippocampal synaptic function and contextual memory
eLife 6:e24192.
https://doi.org/10.7554/eLife.24192
Further reading
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- Neuroscience
The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.
