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Microglial Pruning of Synapses in the Prefrontal Cortex During Adolescence
Allyson P Mallya1, Hui-Dong Wang2, Han Noo Ri Lee1
1Neuroscience Program, Vanderbilt University, Nashville, TN, USA.
Cerebral Cortex (New York, N.Y. : 1991)
|April 19, 2018
Summary
Microglia (MG) prune synapses in the adolescent prefrontal cortex (PFC). This transient synaptic remodeling by MG may contribute to structural brain changes seen in schizophrenia.
Area of Science:
- Neuroscience
- Cell Biology
- Psychiatry
Background:
- Schizophrenia is associated with altered synaptic pruning in the prefrontal cortex (PFC) during adolescence.
- Microglia (MG), the brain's immune cells, are known to sculpt synapses during early development.
- The role of MG in adolescent PFC structural maturation and synaptic pruning remains unclear.
Purpose of the Study:
- To investigate the involvement of microglia (MG) in developmentally specific synapse elimination within the adolescent prefrontal cortex (PFC).
- To determine if MG contribute to the structural maturation of the PFC during this critical developmental period.
Main Methods:
- Layer 5 PFC pyramidal cells (PCs) in rats were intracellularly filled with Lucifer Yellow for dendritic spine analysis at various postnatal days (P24-P50).
- Microglia (MG) engulfment of presynaptic glutamatergic terminals and postsynaptic dendritic spines in the contralateral PFC was evaluated.
- Dendritic spine density and MG phagocytosis of synaptic elements were quantified across developmental stages.
Main Results:
- Dendritic spine density in the PFC peaked around postnatal day 35.
- A significant increase in MG engulfment of dendritic spines was observed at P39, subsiding by P50.
- Microglia (MG) were found to phagocytose both presynaptic glutamatergic terminals and postsynaptic dendritic spines in the adolescent PFC.
Conclusions:
- Microglia (MG) transiently prune synapses of prefrontal cortex (PFC) pyramidal cells during adolescence.
- This MG-mediated synaptic remodeling in the PFC during adolescence may underlie structural neuropathological changes observed in schizophrenia.
- The findings highlight a critical role for microglia in adolescent brain development and its potential link to psychiatric disorders.
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