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

doi:10.1016/j.celrep.2020.108464

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 journal › Article › peer-review

26 Scopus citations

Abstract

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 language	English (US)
Article number	108464
Journal	Cell reports
Volume	33
Issue number	9
DOIs	https://doi.org/10.1016/j.celrep.2020.108464
State	Published - Dec 1 2020

Funding

We thank Martinna Tapies for assistance with mouse breeding and animal care, members of the Prakriya laboratory for helpful discussions, and Priscilla Yeung and Al George for helpful comments on the manuscript. This work was supported by NIH grants R01NS057499 and R01NS115508 to M.P. and R01NS080598 to G.T.S. A.B.T. was supported by NIH predoctoral fellowship F30 NS090817 and the Medical Scientist Training Program . T.I. was supported by a Nippon Medical School grant-in-aid overseas training award and a grant-in-aid award from the Japan Society for the Promotion of Science ( JP 17K16990 ).

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2020.108464

Cite this

Maneshi, M. M., Toth, A. B., Ishii, T., Hori, K., Tsujikawa, S., Shum, A. K., Shrestha, N., Yamashita, M., Miller, R. J., Radulovic, J., Swanson, G. T., & Prakriya, M. (2020). Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca²⁺ Signals in Dendritic Spines to Regulate Working and Associative Memory. Cell reports, 33(9), Article 108464. https://doi.org/10.1016/j.celrep.2020.108464

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

abstract = "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.",

keywords = "CRAC channels, Orai1, STIM1, calcium, dendritic calcium signaling, dendritic spines, learning and memory, long-term potentiation, synaptic plasticity",

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Maneshi, MM, Toth, AB, Ishii, T, Hori, K, Tsujikawa, S, Shum, AK, Shrestha, N, Yamashita, M , Miller, RJ, Radulovic, J, Swanson, GT & Prakriya, M 2020, 'Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca²⁺ Signals in Dendritic Spines to Regulate Working and Associative Memory', Cell reports, vol. 33, no. 9, 108464. https://doi.org/10.1016/j.celrep.2020.108464

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AU - Shrestha, Nisha

AU - Yamashita, Megumi

AU - Miller, Richard J.

AU - Radulovic, Jelena

AU - Swanson, Geoffrey T.

AU - Prakriya, Murali

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