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Culturing Microglia from the Neonatal and Adult Central Nervous System
Published on: August 9, 2013
Microglia control glutamatergic synapses in the adult mouse hippocampus
Bernadette Basilico1, Laura Ferrucci1, Patrizia Ratano2
1Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
Abstract:
Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1-/- mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses.
Insights
Microglia depletion reversibly impairs hippocampal synapses and learning in mice. Restoring microglia recovers synaptic function and cognitive abilities, highlighting their crucial role in adult brain plasticity.
Area of Science:
- Neuroscience
- Cell Biology
- Synaptic Plasticity
Background:
- Microglia are key regulators of synaptic development and plasticity.
- The precise role of microglia in normal adult synaptic function remains unclear.
Purpose of the Study:
- To investigate the impact of pharmacological microglia depletion on hippocampal synapses in adult mice.
- To elucidate the contribution of the CX3CL1/CX3CR1 axis to microglia-mediated synaptic regulation.
Main Methods:
- Pharmacological depletion of microglia using PLX5622 in adult wild-type mice.
- Electrophysiological recordings of hippocampal CA3-CA1 synapses.
- Assessment of dendritic spine density and synaptic morphology.
- Behavioral testing using the Novel Object Recognition task.
- Experiments in Cx3cr1 knockout mice to investigate the CX3CL1/CX3CR1 axis.
Main Results:
- Microglia depletion reduced glutamatergic activity, decreased dendritic spine density, and induced immature synaptic features.
- Synaptic changes were associated with impaired performance in the Novel Object Recognition task.
- PLX5622 effects were absent in Cx3cr1 knockout mice, implicating the CX3CL1/CX3CR1 pathway.
- Microglia repopulation led to the recovery of synaptic function and learning abilities.
Conclusions:
- Microglia are essential for maintaining normal synaptic organization and function in the adult brain.
- Pharmacological depletion of microglia induces reversible synaptic and cognitive deficits.
- The CX3CL1/CX3CR1 axis plays a critical role in microglia's regulation of synaptic plasticity and function.
