Orai1 Channels Are Essential for Amplification of Glutamate-Evoked Ca2+ Signals in Dendritic Spines to Regulate Working and Associative Memory
| Autor: | Shogo Tsujikawa, Megumi Yamashita, Anna B. Toth, Murali Prakriya, Richard J. Miller, Andrew K. Shum, Geoffrey T. Swanson, Nisha Shrestha, Jelena Radulovic, Toshiyuki Ishii, Mohammad Mehdi Maneshi, Kotaro Hori |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Orai1 Dendritic spine ORAI1 Protein STIM1 Cell Glutamic Acid Biology Hippocampal formation Hippocampus General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Mice 0302 clinical medicine Memory medicine Animals Calcium Signaling dendritic calcium signaling lcsh:QH301-705.5 calcium Voltage-dependent calcium channel ORAI1 Chemistry Pyramidal Cells Glutamate receptor Long-term potentiation dendritic spines Content-addressable memory 030104 developmental biology medicine.anatomical_structure nervous system lcsh:Biology (General) Synaptic plasticity Forebrain Excitatory postsynaptic potential CRAC channels Neuroscience 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Cell Reports, Vol 33, Iss 9, Pp 108464-(2020) Cell Reports, Vol 34, Iss 13, Pp 108911-(2021) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. In Brief Ca2+ signals in dendritic spines are critical for synaptic plasticity and cognitive functions. Maneshi et al. show that store-operated Orai1 channels are essential for amplifying neurotransmitter-evoked Ca2+ signals in dendritic spines of mouse hippocampal neurons. This function of Orai1 is crucial for long-term potentiation and hippocampal-dependent learning and memory. Graphical Abstract |
| Databáze: | OpenAIRE |
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