The multilevel exploration test, a novel paradigm to measure exploratory behavior in depression animal models and the involvement of the PL-ZI circuit.
Acta pharmacologica Sinica May 19, 2026 Jun-Nan Xu, Jing-Ting Li, Ru-Xia Xu et al.
Depressed mice show reduced motivation to explore in a new behavioral test called the Multilevel Exploration Test (MET), which breaks exploration into search, attend/investigate, and approach phases. Activating a specific neural circuit from the prelimbic cortex to the zona incerta restored exploratory deficits and alleviated other depression-like behaviors. A machine learning model using MET data predicted individual emotional states—normal, anxiety-like, or depression-like—with over 92% accuracy. The MET offers a high-throughput way to study motivation-related brain mechanisms and may help identify new antidepressant targets.