Spreading depression sends microglia on Lévy flights

Area of Science:

• Neuroscience
• Cell Biology
• Neuroinflammation

Background:

• Spreading depression (SD) is implicated in migraine aura and involves transient synaptic activity loss and altered neuronal excitability.
• Microglia, immune cells in the brain, influence neuronal activity and synaptic scaling through cytokine release.
• While SD affects microglia, the impact of synaptic activity fluctuations on microglial cell movement remains unclear.

Purpose of the Study:

• To investigate microglial cell movement dynamics in response to spreading depression (SD) and varying synaptic activity.
• To determine how synaptic activity levels modulate microglial cell motility and migration patterns.

Main Methods:

• Utilized time-lapse imaging of rat hippocampal slice cultures to observe microglial behavior.
• Manipulated neuronal activity using chemical long-term potentiation, LPS, and tetrodotoxin (TTX).
• Applied glutamate and ATP to mimic synaptic activity restoration.

Main Results:

• Microglial cells exhibited Lévy flight-like movement patterns in uninjured brain tissue.
• SD induced increased microglial cell movement hours after the event, correlating with rising synaptic activity.
• Enhanced neuronal activity decreased microglial movement, whereas activity blockade significantly increased it.
• Restoring synaptic activity with glutamate and ATP halted TTX-induced microglial movement.

Conclusions:

• Synaptic activity retains microglia in place; its absence promotes their movement across wider brain areas.
• Increased microglial movement post-SD may be a prolonged, potentially maladaptive response contributing to migraine susceptibility.
• Targeting activity-dependent microglial movement could offer a novel therapeutic strategy for reducing migraine susceptibility.