The article reviews the role of microglia in the healthy brain, highlighting their dynamic behavior and interactions with neuronal and non-neuronal elements. Microglia, often considered "immune" cells, are found to play crucial roles in postnatal development, adult neuronal plasticity, and circuit function. Key findings include: 1. **Postnatal Development**: Microglia are involved in synaptic pruning, where they phagocytose extranumerary synapses, particularly during the first two weeks of postnatal development. This process is regulated by chemokines like CX3CR1 and involves the complement system, which tags synapses for elimination. 2. **Adult Circuit Plasticity and Function**: Microglia contribute to the phagocytosis of apoptotic newborn neurons in the hippocampus, enhancing neuronal activity through ATP release and purinergic signaling. They also influence synaptic transmission by modulating astrocytic gliotransmission. 3. **Microglial Reorganization of Neuronal Circuits**: Microglia can reorganize neuronal circuits by remodeling the perisynaptic environment and phagocytosing synaptic elements, particularly small dendritic spines, which are more likely to be eliminated. 4. **Regulation of Microglial Distribution, Morphology, and Motility**: Microglial dynamics are influenced by various factors, including ATP, CX3CR1, CD200, and CD47. They exhibit high motility, maintaining overall size and symmetry while avoiding direct contact with neighboring cells. 5. **Microglial Membranes in the Healthy Brain**: The membranes of microglia in the healthy brain likely differ regionally and are influenced by previous immune challenges, affecting their receptor composition and signaling outcomes. Overall, these findings suggest that microglia are important contributors to normal brain physiology, beyond their roles in pathological conditions.The article reviews the role of microglia in the healthy brain, highlighting their dynamic behavior and interactions with neuronal and non-neuronal elements. Microglia, often considered "immune" cells, are found to play crucial roles in postnatal development, adult neuronal plasticity, and circuit function. Key findings include: 1. **Postnatal Development**: Microglia are involved in synaptic pruning, where they phagocytose extranumerary synapses, particularly during the first two weeks of postnatal development. This process is regulated by chemokines like CX3CR1 and involves the complement system, which tags synapses for elimination. 2. **Adult Circuit Plasticity and Function**: Microglia contribute to the phagocytosis of apoptotic newborn neurons in the hippocampus, enhancing neuronal activity through ATP release and purinergic signaling. They also influence synaptic transmission by modulating astrocytic gliotransmission. 3. **Microglial Reorganization of Neuronal Circuits**: Microglia can reorganize neuronal circuits by remodeling the perisynaptic environment and phagocytosing synaptic elements, particularly small dendritic spines, which are more likely to be eliminated. 4. **Regulation of Microglial Distribution, Morphology, and Motility**: Microglial dynamics are influenced by various factors, including ATP, CX3CR1, CD200, and CD47. They exhibit high motility, maintaining overall size and symmetry while avoiding direct contact with neighboring cells. 5. **Microglial Membranes in the Healthy Brain**: The membranes of microglia in the healthy brain likely differ regionally and are influenced by previous immune challenges, affecting their receptor composition and signaling outcomes. Overall, these findings suggest that microglia are important contributors to normal brain physiology, beyond their roles in pathological conditions.