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Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
Published on: January 20, 2015
Dopaminergic signaling regulates microglial surveillance and adolescent plasticity in the mouse frontal cortex
Rianne Stowell1, Kuan Hong Wang2
1Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
Abstract:
Adolescence is a sensitive period for frontal cortical development and cognitive maturation, marked by heightened structural plasticity in the dopaminergic (DA) mesofrontal circuit. However, the cellular and molecular mechanisms underlying this plasticity remain unclear. Here, we show that microglia, the brain's innate immune cells, are highly responsive to mesofrontal DA signaling during adolescence. Longitudinal in vivo two-photon imaging in mice reveals that frontal cortical microglia increase their surveillance of the parenchyma and DA axonal boutons following rewarding experiences or optogenetic stimulation of DA axons. Microglial contacts with DA axons consistently precede bouton formation, and microglia-bouton interactions are regulated by D1- and D2-type DA receptors in adolescence and adulthood. Furthermore, microglial purinergic receptor P2RY12 signaling is necessary for enhanced microglial surveillance and DA bouton formation during adolescence. These results uncover bidirectional interactions between DA signaling and microglial surveillance that drive adolescent frontal plasticity and identify potential targets for restoring plasticity in adulthood.
Insights
Microglia, the brain's immune cells, actively interact with dopamine signaling in the adolescent frontal cortex. This interaction is crucial for brain plasticity and the development of dopamine pathways during this sensitive period.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Adolescence is a critical period for frontal cortical development and cognitive maturation.
- The dopaminergic (DA) mesofrontal circuit exhibits significant structural plasticity during adolescence.
- Cellular and molecular mechanisms driving this adolescent brain plasticity are not fully understood.
Purpose of the Study:
- To investigate the role of microglia in adolescent frontal cortical plasticity.
- To elucidate the interaction between microglia and dopaminergic signaling during adolescence.
- To identify molecular targets for modulating adolescent brain plasticity.
Main Methods:
- Longitudinal in vivo two-photon imaging in mice.
- Optogenetic stimulation of DA axons.
- Assessment of microglial surveillance and DA bouton formation.
- Pharmacological manipulation of DA receptors and P2RY12 signaling.
Main Results:
- Microglia surveillance of the frontal cortex and DA axons increases during adolescence.
- Microglial-DA axon interactions precede DA bouton formation.
- D1 and D2 dopamine receptors regulate microglial-axon interactions.
- P2RY12 signaling in microglia is essential for enhanced surveillance and DA bouton formation.
Conclusions:
- Microglia and DA signaling engage in bidirectional interactions during adolescence.
- These interactions are critical for driving frontal cortical plasticity.
- Targeting microglial P2RY12 signaling may offer therapeutic potential for restoring adolescent brain plasticity in adulthood.
