Related Experiment Video
Updated: Feb 11, 2026
Author Spotlight: Studying Drug Impacts on Brain Signals Using Dual LFP Recording Protocol in Mice
Published on: February 16, 2024
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.
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.
Insights
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.
Related Concept Videos
01:14Role of Cerebellum and Prefrontal Cortex in Memory
02:47The Synapse
01:18Cognitive Development During Adolescence
01:28Electrical Synapses
Gap junctions allow the current to pass directly from one cell to the next. In contrast, in the chemical synapse, the neurotransmitters carry the information through the synaptic cleft from one neuron to the next. They consist of two...
01:26Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...