Nanoscale synaptic remodeling at corticostriatal circuits predicts flexible action control.

ABSTRACT: Synaptic plasticity is a fundamental substrate of behavioral adaptation, yet the underlying molecular dynamics remain poorly defined. We tested the hypothesis that, within striatal circuits, flexibility relies on nanoscale remodeling of synaptic machinery coupling anterograde glutamatergic transmission to retrograde endocannabinoid signaling, a process disrupted in states of rigidity and aging. In the dorsolateral striatum, we found cell-type-specific facilitation of metabotropic glutamate receptor 5 (mGlu₅)-dependent, endocannabinoid-mediated long-term depression at cortico-striatal synapses of indirect pathway neurons in flexible goal-directed behavior, but not after training promoting inflexibility. Stochastic Optical Reconstruction Microscopy (STORM) super-resolution imaging

SUBMITTER: Paget-Blanc V 

PROVIDER: S-EPMC12636460 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature