Astrocytic cAMP modulates memory via synaptic plasticity

Zhiwen Zhou, Kazuki Okamoto, Junya Onodera, Toshimitsu Hiragi, Megumi Andoh, Masahito Ikawa, Kenji F. Tanaka, Yuji Ikegaya, Ryuta Koyama

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere2016584118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number3
DOIs
Publication statusPublished - 2021 Jan 15

Keywords

  • Astrocyte
  • CAMP
  • Memory
  • PAC
  • Synapse

ASJC Scopus subject areas

  • General

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