Altered synaptic connectivity and brain function in mice lacking microglial adapter protein Iba1.

Area of Science:

• Neuroscience
• Cell Biology
• Genetics

Background:

• Microglia are key immune cells in the brain, regulating synaptic plasticity and function.
• Ionized calcium-binding adapter protein 1 (Iba1), encoded by the Allograft inflammatory factor 1 (Aif1) gene, is a known microglial marker but its functional role is unclear.

Purpose of the Study:

• To investigate the functional role of Iba1 in microglial activity, synaptic development, and behavior using Iba1-deficient mice.
• To characterize the impact of Iba1 deficiency on microglial morphology, synaptic structure, and associated behaviors.

Main Methods:

• Utilized global Iba1-deficient (Aif1-/-) mice for experiments.
• Performed microglial imaging in acute hippocampal slices and fixed tissues.
• Conducted biochemical assays to analyze protein expression.
• Assessed synaptic function and number using neuronal labeling and whole-cell patch-clamp recordings.
• Evaluated behavioral changes in object recognition memory and social interaction.

Main Results:

• Aif1-/- microglia showed reduced motility and ramification.
• Altered expression of microglial-enriched proteins involved in synaptic pruning was observed in Aif1-/- brain tissues.
• Juvenile Aif1-/- mice exhibited deficits in excitatory synapse number and synaptic drive.
• Microglial synaptic engulfment capacity was diminished in juvenile Aif1-/- mice.
• Postnatal synaptic deficits persisted into adulthood, correlating with impaired object recognition memory and social interaction.

Conclusions:

• Iba1 plays a critical role in excitatory synaptic growth during early brain development.
• Iba1 deficiency leads to persistent synaptic deficits and significant behavioral impairments.
• These findings underscore Iba1's importance in microglial functions essential for neurodevelopment and behavior.