Advances in neurological disease models and optimization of the laboratory animal environment for reproducible research.

Animal models of neurological diseases have evolved from phenotype-based systems to integrated platforms that link genetics, molecular signaling, synaptic physiology, neural circuits, behavior, and therapeutic responses. Simultaneously, increasingly precise phenotyping has revealed that experimental outcomes are strongly influenced by age, microbiological status, diet, housing, stress, previous experience, health status, and measurement methodology. This review considers these two developments to be complementary requirements for reliable experimental neuroscience. Studies on voltage-gated calcium channel mutants have shown that defined genetic alterations can produce age-dependent abnormalities in motor function, cognition, emotion, autonomic regulation, and seizure susceptibility. Studies on N-methyl-D-aspartate (NMDA) receptor-Calcium-calmodulin-dependent protein kinase II (CaMKII) signaling, epigenetic regulators, stress-related phenotypes, and fear memory circuits have further illustrated how animal models can be characterized across levels, from molecular mechanisms to neural ensembles and therapeutic rescues. Translation to common marmosets extends these approaches to primate sleep and epilepsy, while highlighting the effects of genetic diversity, spontaneous disease, handling, and colony management. In parallel, studies on germ-free animals, diet, the gut microbiota, barrier facilities, cage enrichment, telemetry, and veterinary monitoring have demonstrated that husbandry variables, rather than technical background, are biological determinants. Integrating rigorous disease model characterization with evidence-based husbandry, environmental control, and transparent reporting should improve the reproducibility and translational value of preclinical neuroscience research and the welfare of the animals used.