Synapse-specific astrocyte gating of amygdala-related behavior

Nat Neurosci. 2017 Nov;20(11):1540-1548. doi: 10.1038/nn.4649. Epub 2017 Sep 25.

Abstract

The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Adenosine A2 Receptor Antagonists / pharmacology
  • Amygdala / cytology
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Fear / drug effects
  • Fear / physiology*
  • Fear / psychology
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Net / cytology
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Organ Culture Techniques
  • Receptor, Adenosine A2A / physiology
  • Synapses / drug effects
  • Synapses / physiology*

Substances

  • Adenosine A2 Receptor Antagonists
  • Receptor, Adenosine A2A
  • 6-Cyano-7-nitroquinoxaline-2,3-dione