Prefrontal Cortex Development in Health and Disease: Lessons from Rodents and Humans

Trends Neurosci. 2021 Mar;44(3):227-240. doi: 10.1016/j.tins.2020.10.017. Epub 2020 Nov 24.


The role of the prefrontal cortex (PFC) takes center stage among unanswered questions in modern neuroscience. The PFC has a Janus-faced nature: it enables sophisticated cognitive and social abilities that reach their maximum expression in humans, yet it underlies some of the devastating symptoms of psychiatric disorders. Accordingly, appropriate prefrontal development is crucial for many high-order cognitive abilities and dysregulation of this process has been linked to various neuropsychiatric diseases. Reviewing recent advances in the field, with a primary focus on rodents and humans, we highlight why, despite differences across species, a cross-species approach is a fruitful strategy for understanding prefrontal development. We briefly review the developmental contribution of molecules and extensively discuss how electrical activity controls the early maturation and wiring of prefrontal areas, as well as the emergence and refinement of input-output circuitry involved in cognitive processing. Finally, we highlight the mechanisms of developmental dysfunction and their relevance for psychiatric disorders.

Keywords: adolescence; autism; development; memory; molecular cues; network oscillations; prefrontal; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Mental Disorders*
  • Prefrontal Cortex
  • Rodentia*