Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca2+ Signals in Dendritic Spines to Regulate Working and Associative Memory

Mohammad Mehdi Maneshi, Anna B. Toth, Toshiyuki Ishii, Kotaro Hori, Shogo Tsujikawa, Andrew K. Shum, Nisha Shrestha, Megumi Yamashita, Richard J. Miller, Jelena Radulovic, Geoffrey T. Swanson, Murali Prakriya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Store-operated Orai1 calcium channels function as highly Ca2+-selective ion channels and are broadly expressed in many tissues including the central nervous system, but their contributions to cognitive processing are largely unknown. Here, we report that many measures of synaptic, cellular, and behavioral models of learning are markedly attenuated in mice lacking Orai1 in forebrain excitatory neurons. Results with focal glutamate uncaging in hippocampal neurons support an essential role of Orai1 channels in amplifying NMDA-receptor-induced dendritic Ca2+ transients that drive activity-dependent spine morphogenesis and long-term potentiation at Schaffer collateral-CA1 synapses. Consistent with these signaling roles, mice lacking Orai1 in pyramidal neurons (but not interneurons) exhibit striking deficits in working and associative memory tasks. These findings identify Orai1 channels as essential regulators of dendritic spine Ca2+ signaling, synaptic plasticity, and cognition.

Original languageEnglish (US)
Article number108464
JournalCell reports
Issue number9
StatePublished - Dec 1 2020


  • CRAC channels
  • Orai1
  • STIM1
  • calcium
  • dendritic calcium signaling
  • dendritic spines
  • learning and memory
  • long-term potentiation
  • synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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