Microglial Pruning of Synapses in the Prefrontal Cortex During Adolescence

Abstract Exaggerated synaptic elimination in the prefrontal cortex (PFC) during adolescence has been suggested to contribute to the neuropathological changes of schizophrenia. Recent data indicate that microglia (MG) sculpt synapses during early postnatal development. However, it is not known if MG...

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Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2019-04, Vol.29 (4), p.1634-1643
Main Authors: Mallya, Allyson P, Wang, Hui-Dong, Lee, Han Noo Ri, Deutch, Ariel Y
Format: Article
Language:English
Subjects:
Animals
Dendritic Spines - physiology
Female
Male
Microglia - cytology
Microglia - physiology
Original
Prefrontal Cortex - cytology
Prefrontal Cortex - growth & development
Pyramidal Cells - cytology
Pyramidal Cells - physiology
Rats, Sprague-Dawley
Synapses - physiology
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Summary:Abstract Exaggerated synaptic elimination in the prefrontal cortex (PFC) during adolescence has been suggested to contribute to the neuropathological changes of schizophrenia. Recent data indicate that microglia (MG) sculpt synapses during early postnatal development. However, it is not known if MG contribute to the structural maturation of the PFC, which has a protracted postnatal development. We determined if MG are involved in developmentally specific synapse elimination in the PFC, focusing on adolescence. Layer 5 PFC pyramidal cells (PCs) were intracellularly filled with Lucifer Yellow for dendritic spine measurements in postnatal day (P) 24, P30, P35, P39, and P50 rats. In the contralateral PFC we evaluated if MG engulfed presynaptic (glutamatergic) and postsynaptic (dendritic spines) elements. Dendritic spine density increased from P24 to P35, when spine density peaked. There was a significant increase in MG engulfment of spines at P39 relative to earlier ages; this subsided by P50. MG also phagocytosed presynaptic glutamatergic terminals. These data indicate that MG transiently prune synapses of PFC PCs during adolescence, when the symptoms of schizophrenia typically first appear. An increase in MG-mediated synaptic remodeling of PFC PCs may contribute to the structural changes observed in schizophrenia.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bhy061