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Astrocytic cAMP modulates memory via synaptic plasticity.


ABSTRACT: Astrocytes play a key role in brain homeostasis and functions such as memory. Specifically, astrocytes express multiple receptors that transduce signals via the second messenger cAMP. However, the involvement of astrocytic cAMP in animal behavior and the underlying glial-neuronal interactions remains largely unknown. Here, we show that an increase in astrocytic cAMP is sufficient to induce synaptic plasticity and modulate memory. We developed a method to increase astrocytic cAMP levels in vivo using photoactivated adenylyl cyclase and found that increased cAMP in hippocampal astrocytes at different time points facilitated memory formation but interrupted memory retention via NMDA receptor-dependent plasticity. Furthermore, we found that the cAMP-induced modulation of memory was mediated by the astrocyte-neuron lactate shuttle. Thus, our study unveils a role of astrocytic cAMP in brain function by providing a tool to modulate astrocytic cAMP in vivo.

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC7826339 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Astrocytic cAMP modulates memory via synaptic plasticity.

Zhou Zhiwen Z   Okamoto Kazuki K   Onodera Junya J   Hiragi Toshimitsu T   Andoh Megumi M   Ikawa Masahito M   Tanaka Kenji F KF   Ikegaya Yuji Y   Koyama Ryuta R  

Proceedings of the National Academy of Sciences of the United States of America 20210101 3


Astrocytes play a key role in brain homeostasis and functions such as memory. Specifically, astrocytes express multiple receptors that transduce signals via the second messenger cAMP. However, the involvement of astrocytic cAMP in animal behavior and the underlying glial-neuronal interactions remains largely unknown. Here, we show that an increase in astrocytic cAMP is sufficient to induce synaptic plasticity and modulate memory. We developed a method to increase astrocytic cAMP levels in vivo u  ...[more]

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