ドーパミンが選択しアストロサイトが洗練する:運動学習回路再編の新機構(Dopamine Selects, Astrocytes Refine: A New Mechanism for Motor-learning Circuit Rewiring)

2026-02-24 韓国基礎科学研究院(IBS)

Figure 1. Astrocyte-mediated synapse elimination before and after motor learning

<関連情報>

• https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do?nttId=26541&pageIndex=1&searchCnd=&searchWrd=#toggle
• https://www.nature.com/articles/s41467-026-69129-1

運動学習とドーパミン依存性線条体シナプス可塑性はアストロサイトのMEGF10によって制御される Motor learning and dopamine-dependent striatal synaptic plasticity are controlled by astrocytic MEGF10

Young-Jin Choi,Youngeun Lina Lee,Yemin Kim,Jaeseon Jeon,Jae-Ick Kim & Won-Suk Chung
Nature Communications  Published:23 February 2026
DOI:https://doi.org/10.1038/s41467-026-69129-1

Abstract

Dopamine regulates motor learning by modulating striatal synaptic plasticity in medium spiny neurons (MSNs). Despite its well-established role in synaptic plasticity, dopamine’s involvement in glia-mediated synapse remodeling remains unclear. Here, we demonstrate that the astrocytic phagocytic receptor MEGF10 (Multiple Epidermal Growth Factor-like Domains Protein 10), but not MERTK (MER Proto-Oncogene, Tyrosine Kinase), is required for the elimination of corticostriatal excitatory synapses on MSNs during motor learning. Deletion of astrocytic Megf10 impaired long-term potentiation and depression (LTP and LTD), and reduced learning-induced increases in synaptic strength. Notably, chemogenetic activation of corticostriatal transmission or dopamine release from the substantia nigra pars compacta (SNc) selectively enhanced astrocytic synapse elimination. Furthermore, elevated dopamine and motor learning differentially regulated postsynaptic elimination in MSNs depending on dopamine receptor subtype, leading to MEGF10-dependent changes in synaptic remodeling and quantal properties. These findings identify astrocytic MEGF10 as a key mediator of dopamine- and activity-dependent synapse remodeling in the striatum.