Microglia regulate nucleus accumbens synaptic development and circuit function underlying threat avoidance behaviors in mice
In the authors' words
Abstract While microglia are well known for pruning synapses during neurodevelopment, their role in synapse formation remains understudied. Here we investigate how microglial absence impacts synaptic development in the nucleus accumbens (NAc), a region critical for emotional regulation and motivated behaviors. Using genetically modified mice lacking microglia ( Csf1r ΔFIRE/ΔFIRE ), we find blunted excitatory synapse formation in the NAc, particularly during the second and third postnatal weeks. Tissue-level NAc proteomics in the third postnatal week reveals changes in proteins involved in synapse structure, trans-synaptic signaling, and pre-synaptic function. Although electrophysiological changes largely resolve by adulthood, microglia-lacking mice exhibit persistent changes in threat avoidance behavior and underlying NAc neuronal activity. Transient depletion of NAc microglia during the second postnatal week similarly disrupts synapse formation and adult threat avoidance. Together, these findings identify a role for microglia in shaping NAc synaptic development and in establishing functional circuits that support adult behavioral function.
Appeared: Monday, September 28. Nature Communications. Peer-reviewed journal.