Multidimensional behavioral endpoints in zebrafish: Toward integrative neurotoxicity assessment under environmental...

Environmental neurotoxicants often occur at low concentrations, sublethal levels, and in complex scenarios, where traditional physiological or molecular endpoints struggle to detect their subtle effects. Meanwhile, reliance on single behavioral metrics leads to inconsistent and poorly comparable results across studies. This review synthesizes advances in zebrafish behavioral research and proposes a mechanistic multidimensional behavioral integration framework, which unifies anxiety-like behavior, social distance, locomotor trajectory dynamics, and learning and memory into a coherent analytical system. Using metal-induced neurotoxicity, pharmacological modulation of anxiety thresholds, and social buffering of stress responses as examples, we illustrate how this framework enables mechanistic interpretation by linking behavioral phenotypes with neurotransmitter systems, neural circuit dynamics, and molecular stress pathways.The study demonstrates that integrating multiple behavioral dimensions significantly enhances sensitivity to low-dose, nonlinear, and sublethal neurotoxic effects, resolving trajectory distortions, social withdrawal, and cognitive impairments often missed by conventional parameters. Social context emerges as a critical environmental modifier that reshapes neurobehavioral dose-response relationships, independent of classical endocrine indicators. This framework advances behavioral phenotyping from descriptive assessment toward predictive environmental neurotoxicology, providing a scalable and mechanistically grounded strategy for the early detection of neurofunctional perturbations under environmentally realistic exposure conditions.