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Ex Vivo Optogenetic Dissection of Fear Circuits in Brain Slices
Published on: April 5, 2016
Microglia-dependent regulation of fear memory extinction
Yunlong Liu1, Jiaoyang Wo1,2, Emily E Kramer1
1Neuroscience and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada.
Abstract:
Traumatic events produce enduring memories that may be attenuated through extinction learning. Previous work has identified neuronal mechanisms underlying extinction learning that involve the remodeling or inhibition of neuronal ensembles (or engrams) that support the original fear memory. Here we identify a role for microglia in extinction learning in mice. We show that, during extinction, microglia are recruited to the soma and dendritic processes of fear engram neurons in the dentate gyrus. Interactions between microglia and somata mediate transient silencing of engram neurons. Inhibition of microglial recruitment to somata attenuated extinction-induced reductions in engram reactivity and slowed extinction. By contrast, interactions between microglia and dendritic processes promote engulfment of engram synapses and remodeling of engram neurons. Blocking complement signaling in engram neurons prevented extinction-induced engram neuron remodeling and slowed extinction. Together, these findings identify microglia as key regulators of fear engram expression and remodeling during extinction learning.
Insights
Microglia, immune cells in the brain, regulate fear memory extinction by interacting with neurons. These interactions silence fear engram neurons and remodel neural circuits, aiding memory attenuation.
Area of Science:
- Neuroscience
- Immunology
- Memory Research
Background:
- Traumatic events create lasting fear memories.
- Extinction learning can reduce fear memories by modifying neuronal ensembles (engrams).
- Neuronal mechanisms for fear memory extinction are partially understood.
Purpose of the Study:
- To investigate the role of microglia in fear memory extinction.
- To elucidate how microglia interact with fear engram neurons during extinction learning.
Main Methods:
- Studied microglia recruitment to fear engram neurons in the dentate gyrus of mice during extinction learning.
- Examined microglial interactions with neuronal somata and dendritic processes.
- Assessed the impact of inhibiting microglial recruitment and complement signaling on extinction and engram remodeling.
Main Results:
- Microglia were recruited to both somata and dendrites of fear engram neurons.
- Microglia-somata interactions transiently silenced engram neurons, while microglia-dendrite interactions promoted synapse engulfment and neuron remodeling.
- Inhibiting microglial recruitment or complement signaling impaired extinction and engram remodeling.
Conclusions:
- Microglia play a crucial role in regulating fear memory extinction.
- Microglia modulate fear engram expression and structural remodeling through distinct interactions with neuronal compartments.
- Targeting microglial pathways may offer novel therapeutic strategies for fear-related disorders.
