Astrocytic cAMP modulates memory via synaptic plasticity

Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):e2016584118. doi: 10.1073/pnas.2016584118.


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.

Keywords: PAC; astrocyte; cAMP; memory; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclases / genetics*
  • Adenylyl Cyclases / metabolism
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism*
  • Cell Communication
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cyclic AMP / metabolism*
  • Gene Expression Regulation
  • Genes, Reporter
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Lactic Acid / metabolism
  • Light
  • Memory / physiology*
  • Mice
  • Mice, Transgenic
  • Neuronal Plasticity / genetics*
  • Neurons / cytology
  • Neurons / metabolism*
  • Optogenetics
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Stereotaxic Techniques
  • Synapses / metabolism
  • Time Factors


  • Receptors, N-Methyl-D-Aspartate
  • Green Fluorescent Proteins
  • Lactic Acid
  • Cyclic AMP
  • Adenylyl Cyclases