Selective regulation of corticostriatal synapses by astrocytic phagocytosis

• Published in: Nature communications Vol. 16; no. 1; pp. 2504 - 12
• Main Authors: Kim, Ji-young, Kim, Hyeyeon, Chung, Won-Suk, Park, Hyungju
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.03.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 42/44; 45/41; 631/378/2591/2592; 631/378/2596/1308; 631/378/3920; 64/110; 82/51; 9/30; 9/74; Animal models; Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - physiology; Brain; Caudate-putamen; Cerebral Cortex - cytology; Cerebral Cortex - physiology; Corpus Striatum - cytology; Corpus Striatum - metabolism; Corpus Striatum - physiology; Homeostasis; Humanities and Social Sciences; Learning; Long-term potentiation; Long-Term Potentiation - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor skill; Motor skill learning; multidisciplinary; Neostriatum; Neural networks; Neuronal Plasticity - physiology; Phagocytes; Phagocytosis; Phagocytosis - physiology; Plastic properties; Plasticity; Receptors; Science; Science (multidisciplinary); Synapses; Synapses - metabolism; Synapses - physiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-025-57577-0

In the adult brain, neural circuit homeostasis depends on the constant turnover of synapses via astrocytic phagocytosis mechanisms. However, it remains unclear whether this process occurs in a circuit-specific manner. Here, we reveal that astrocytes target and eliminate specific type of excitatory synapses in the striatum. Using model mice lacking astrocytic phagocytosis receptors in the dorsal striatum, we found that astrocytes constantly remove corticostriatal synapses rather than thalamostriatal synapses. This preferential elimination suggests that astrocytes play a selective role in modulating corticostriatal plasticity and functions via phagocytosis mechanisms. Supporting this notion, corticostriatal long-term potentiation and the early phase of motor skill learning are dependent on astrocytic phagocytic receptors. Together, our findings demonstrate that astrocytes contribute to the connectivity and plasticity of the striatal circuit by preferentially engulfing a specific subset of excitatory synapses within brain regions innervated by multiple excitatory sources. Neural circuit homeostasis depends on astrocytic phagocytosis, but its circuit specificity remains unclear. Here, the authors show that astrocytes selectively eliminate corticostriatal synapses, regulating striatal plasticity and motor learning.