Motor learning and dopamine-dependent striatal synaptic plasticity are controlled by astrocytic MEGF10.

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 compa

SUBMITTER: Choi YJ 

PROVIDER: S-EPMC12929717 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature