STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses

Kenrick An Fu Yap, Mahesh Shivarama Shetty, Gisela Garcia-Alvarez, Bo Lu, Durgadevi Alagappan, Masatsugu Oh-Hora, Sreedharan Sajikumar, Marc Fivaz

    Research output: Contribution to journalArticle

    9 Citations (Scopus)

    Abstract

    STIM2 is an integral membrane protein of the endoplasmic reticulum (ER) that regulates the activity of plasma membrane (PM) channels at ER-PM contact sites. Recent studies show that STIM2 promotes spine maturation and surface expression of the AMPA receptor (AMPAR) subunit GluA1, hinting at a probable role in synaptic plasticity. Here, we used a Stim2 cKO mouse to explore the function of STIM2 in Long-Term Potentiation (LTP) and Depression (LTD), two widely-studied models of synaptic plasticity implicated in information storage. We found that STIM2 is required for the stable expression of both LTP and LTD at CA3-CA1 hippocampal synapses. Altered plasticity in Stim2 cKO mice is associated with subtle alterations in the shape and density of dendritic spines in CA1 neurons. Further, surface delivery of GluA1 in response to LTP-inducing chemical manipulations was markedly reduced in excitatory neurons derived from Stim2 cKO mice. GluA1 endocytosis following chemically-induced LTD was also impaired in Stim2 cKO neurons. We conclude that STIM2 facilitates synaptic delivery and removal of AMPARs and regulates activity-dependent changes in synaptic strength through a unique mode of communication between the ER and the synapse.

    Original languageEnglish
    Pages (from-to)54-61
    Number of pages8
    JournalNeurobiology of Learning and Memory
    Volume138
    DOIs
    Publication statusPublished - Feb 1 2017

    All Science Journal Classification (ASJC) codes

    • Experimental and Cognitive Psychology
    • Cognitive Neuroscience
    • Behavioral Neuroscience

    Fingerprint Dive into the research topics of 'STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses'. Together they form a unique fingerprint.

  • Cite this

    Yap, K. A. F., Shetty, M. S., Garcia-Alvarez, G., Lu, B., Alagappan, D., Oh-Hora, M., Sajikumar, S., & Fivaz, M. (2017). STIM2 regulates AMPA receptor trafficking and plasticity at hippocampal synapses. Neurobiology of Learning and Memory, 138, 54-61. https://doi.org/10.1016/j.nlm.2016.08.007