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Published on: July 17, 2017
Glial remodeling enhances short-term memory performance in Wistar rats
Simone N De Luca1, Alita Soch1, Luba Sominsky1
1School of Health and Biomedical Sciences RMIT University, Melbourne, VIC, 3083, Australia.
Background:
Microglia play a key role in neuronal circuit and synaptic maturation in the developing brain. In the healthy adult, however, their role is less clear: microglial hyperactivation in adults can be detrimental to memory due to excessive synaptic pruning, yet learning and memory can also be impaired in the absence of these cells. In this study, we therefore aimed to determine how microglia contribute to short-term memory in healthy adults.
Methods:
To this end, we developed a Cx3cr1-Dtr transgenic Wistar rat with a diphtheria toxin receptor (Dtr) gene inserted into the fractalkine receptor (Cx3cr1) promoter, expressed on microglia and monocytes. This model allows acute microglial and monocyte ablation upon application of diphtheria toxin, enabling us to directly assess microglia's role in memory.
Results:
Here, we show that short-term memory in the novel object and place recognition tasks is entirely unaffected by acute microglial ablation. However, when microglia repopulate the brain after depletion, learning and memory performance in these tasks is improved. This transitory memory enhancement is associated with an ameboid morphology in the newly repopulated microglial cells and increased astrocyte density that are linked with a higher density of mature hippocampal synaptic spines and differences in pre- and post-synaptic markers.
Conclusions:
These data indicate that glia play a complex role in the healthy adult animal in supporting appropriate learning and memory and that subtle changes to the function of these cells may strategically enhance memory.
Insights
Microglia depletion did not affect short-term memory in adult rats. However, repopulating microglia transiently enhanced memory, suggesting glia strategically support learning and memory.
Area of Science:
- Neuroscience
- Cell Biology
- Cognitive Science
Background:
- Microglia are crucial for brain development and synaptic maturation.
- Their role in adult memory is complex, with potential detrimental effects from hyperactivation but impairment in their absence.
- This study investigates microglia's contribution to short-term memory in healthy adults.
Purpose of the Study:
- To determine the role of microglia in short-term memory in healthy adult rats.
- To investigate the effects of acute microglial ablation and subsequent repopulation on memory.
Main Methods:
- Developed a Cx3cr1-Dtr transgenic Wistar rat model for diphtheria toxin-induced microglial and monocyte ablation.
- Assessed short-term memory using novel object and place recognition tasks before and after microglial depletion and repopulation.
Main Results:
- Acute microglial ablation did not impact short-term memory performance.
- Memory performance improved during microglial repopulation, linked to ameboid microglial morphology and increased astrocyte density.
- Enhanced memory correlated with increased mature hippocampal synaptic spines and altered synaptic marker expression.
Conclusions:
- Glia play a multifaceted role in supporting learning and memory in adult animals.
- Subtle modulation of microglial function can strategically enhance memory capabilities.
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