Microglia enhance post-anesthesia neuronal activity by shielding inhibitory synapses

Area of Science:

• Neuroscience
• Immunology
• Anesthesiology

Background:

• Microglia are key immune cells in the central nervous system, crucial for brain homeostasis.
• Anesthesia alters microglia behavior, increasing their interaction with neurons, but the functional impact remains unclear.

Purpose of the Study:

• To investigate the functional significance of microglial process dynamics and neuronal interactions during and after anesthesia.

Main Methods:

• In vivo two-photon imaging in mice to observe microglia and neuronal activity.
• Electron microscopy for detailed synaptic reconstruction.
• Microglial ablation and genetic manipulation (β2-adrenergic receptor knockout) to assess functional roles.

Main Results:

• Microglia processes actively surveil neurons and interact with GABAergic boutons under anesthesia.
• Microglial processes were found within the synaptic cleft, shielding inhibitory inputs.
• Post-anesthesia neuronal hyperactivity was observed, directly contacted by microglia processes.
• Microglial ablation or loss of β2-adrenergic receptors abolished post-anesthesia hyperactivity.

Conclusions:

• Microglial process dynamics play a critical role in modulating neuronal activity during anesthesia recovery.
• Microglia transiently enhance post-anesthesia neuronal activity by physically shielding inhibitory GABAergic inputs.
• This shielding mechanism highlights a novel function of microglia in regulating brain states affected by anesthesia.