Microglia mediate forgetting via complement-dependent synaptic elimination

Area of Science:

• Neuroscience
• Immunology
• Memory Research

Background:

• Synapses in engram cells are crucial for memory storage.
• Memory loss is associated with the weakening or loss of these synapses.
• Microglia, the brain's immune cells, are implicated in synaptic plasticity.

Purpose of the Study:

• To investigate the role of microglia in the forgetting of remote memories.
• To elucidate the mechanisms by which microglia contribute to memory degradation.
• To determine if complement pathways are involved in microglial-mediated forgetting.

Main Methods:

• Observation of microglial engulfment of synaptic components in mouse hippocampi.
• Depletion of microglia and inhibition of microglial phagocytosis.
• Introduction of CD55 to inhibit complement pathways in engram cells.
• Assessment of memory retention and engram cell dissociation.

Main Results:

• Microglial engulfment of synaptic components was observed in healthy adult mice.
• Depleting microglia or inhibiting their phagocytosis prevented memory forgetting.
• Inhibition of complement pathways in engram cells also prevented forgetting.
• Microglia were involved in both neurogenesis-related and unrelated memory degradation.

Conclusions:

• Microglia eliminate synapses in a complement-dependent and activity-dependent manner, leading to memory forgetting.
• Complement-dependent synapse elimination by microglia is a key mechanism for the forgetting of remote memories.
• Targeting microglial activity and complement pathways may offer strategies to combat memory loss.