An ace in the hole? Opportunities and limits of using mice to understand schizophrenia neurobiology

In applying model organisms to study the neurobiology of mental disorders, rodents offer unique potential for probing, with high spatiotemporal resolution, the neural and molecular mechanisms underlying behavior in a mammalian system. Furthermore, investigators can wield exceptional power to manipulate genes, molecules, and circuits in mice to pin down causal relationships. While these advantages have allowed us to understand much more deeply than ever before the brain mechanisms regulating complex behaviors, the impact of rodent models on developing therapeutic strategies for psychiatric disorders has remained thus far limited. Herein, we will discuss the opportunities and limits of using mouse models in the context of schizophrenia, a complex psychiatric disorder with strong genetic basis that poses various unmet clinical needs calling out for basic science research. We review approaches for employing behavioral, genetic, and circuit-based methods in rodents to inform schizophrenia symptomatology, pathophysiology, and, ultimately, treatment.