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

https://doi.org/10.1016/j.tins.2020.10.017Get rights and content
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Highlights

  • The prefrontal cortex (PFC) comprises a conglomeration of brain areas with a largely heterogeneous cross-species anatomical definition that accounts for numerous cognitive abilities.

  • Abnormal structure and function of the PFC is linked to lower performance in various cognitive domains and is associated with several neuropsychiatric diseases.

  • Prefrontal development, while protracted compared with sensory cortices, is similarly controlled by molecular cues that set the proliferation, migration, differentiation, and eventual boundaries of prefrontal neurons.

  • During development, under the driving force of the hippocampus and thalamic nuclei, prefrontal circuits start to generate characteristic patterns of coordinated electrical activity that dynamically change with age in their cellular mechanisms, spectral structure, and synchrony.

  • Patterns of electrical activity and connectivity underlie the reorganization of prefrontal areas in line with the maturation of cognitive abilities, such as working memory and decision making.

  • Miswiring of prefrontal areas, resulting from genetic factors or environmental stressors acting during development, can contribute to cognitive impairment in psychiatric disorders.

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

prefrontal
development
network oscillations
molecular cues
schizophrenia
autism
memory
adolescence

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