Transcranial Alternating Current Stimulation Improves Post-Anesthesia Motor Function in Aged Mice via Dual striatal Pathways: Dopamine Release and THIN Activation

Background: Transcranial alternating current stimulation (tACS) enhances motor performance, but its subcortical mechanisms in aged populations remain unclear. We investigated whether 20 Hz tACS over M1 engages striatal circuitry in aged mice under sevoflurane anesthesia via two parallel mechanisms: nigrostriatal dopamine release and THIN activation. Methods: Aged mice received 20 Hz tACS (0.15 mA, 20 min/day) or sham over M1 for seven days under sevoflurane. Motor performance was assessed by single‑pellet reaching task. Analyses included: FSCV for dopamine release; Golgi staining for spine density; c‑Fos/TH for THIN activation; EEG and cortical blood flow (CBF). Optogenetic gain‑of‑function with selective 20 Hz THIN activation was performed in a separate cohort. Results:tACS improved post‑anesthesia reaching success (p < 0.05), enhanced dopamine release (p < 0.01), THIN activation (p < 0.01), spine density (p < 0.01), and β‑band oscillations (p < 0.01). Optogenetic THIN activation recapitulated motor and β‑band enhancement (both p < 0.01), but not CBF increase. Conclusion: 20 Hz tACS enhances motor function in aged mice under sevoflurane via dopamine‑dependent plasticity and THIN‑mediated oscillatory modulation, identifying THINs as a key cellular substrate for tACS‑induced motor