Neurodevelopmental disorders, and more generally CNS development, are extraordinarily difficult to study for several reasons. Rodent models of brain development have proved insightful, but are limited by their lack of complexity and sophistication compared to the human brain, especially the human cortex. Mice and rats are estimated to have 3–4 orders of magnitude fewer neurons than humans1, and, owing to non-linear scaling of neuronal density and connections with brain size, the development and structure of the human brain differs considerably from that of a rodent’s. The development of rodent brains is also much faster than that of humans. As a result, the prefrontal and temporal cortices, along with other interconnected association areas, are highly-developed in humans compared with rodents2; these areas are often associated with higher cognitive functions such as language, planning, logical thought, expression of personality and emotions and are regions that are most relevant to neurodevelopmental disorders. The lack of efficacious CNS drugs discovered via rodent models supports the idea that preclinical animal models of neurodevelopmental disorders have limited validity 3–6.
