Dopaminergic signaling regulates microglial surveillance and adolescent plasticity in the frontal cortex.
bioRxiv
; 2024 Mar 13.
Article
in En
| MEDLINE
| ID: mdl-38559264
ABSTRACT
Adolescence is a sensitive period for frontal cortical development and cognitive maturation. The dopaminergic (DA) mesofrontal circuit is particularly malleable in response to changes in adolescent experience and DA activity. However, the cellular mechanisms engaged in this plasticity remain unexplored. Here, we report that microglia, the innate immune cells of the brain, are uniquely sensitive to adolescent mesofrontal DA signaling. Longitudinal in vivo two-photon imaging in mice shows that frontal cortical microglia respond dynamically to plasticity-inducing behavioral or optogenetic DA axon stimulation with increased parenchymal and DA bouton surveillance. Microglial-axon contact precedes new bouton formation, and both D1 and D2-type DA receptors regulate microglial-bouton interactions and axonal plasticity. Moreover, D2 antagonism in adults reinstates adolescent plasticity, including increased microglial surveillance and new DA bouton formation. Our results reveal that DA signaling regulates microglial surveillance and axonal plasticity uniquely in the adolescent frontal cortex, presenting potential interventions for restoring plasticity in the adult brain.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
BioRxiv
Year:
2024
Document type:
Article