Online Lecture by Ileana Hanganu-Opatz

Prefrontal cortex: hub of cognitive development

The prefrontal cortex acts as a hub of cognitive processing indispensable for the daily life, yet its development is poorly understood. Disruption of prefrontal-dependent short-term memory and executive performance is the major burden of neuropsychiatric diseases, such as schizophrenia and autism spectrum disorders. The absence of a clear understanding of their pathophysiology has resulted in primarily symptom-based treatments with low response rates. Many of the genes and risk factors associated with neuropsychiatric diseases regulate brain development, leading to the hypothesis that abnormal maturation causes impaired network function and ultimately poor cognitive abilities later in life. Indeed, we provide evidence that rhythmic network activity of prefrontal circuits is already compromised in prodromal patients and during early postnatal development in mouse models of schizophrenia and autism.

Towards a better understanding of how neuronal activity regulates the development of prefrontal networks, we developed novel techniques to monitor and manipulate this activity from birth until adulthood. Early in life, the activity of rodent prefrontal cortex is coordinated in oscillatory patterns, yet, in line with the delayed structural maturation and emergence of cognitive abilities, they appear later than in other cortical areas. Inputs from cortical and subcortical areas boost the activation of local prefrontal circuits. Moreover, intracortical interactions lead to the emergence of oscillatory activity at fast frequencies. We provide first evidence that activity during defined developmental time windows is necessary for the maturation of prefrontal function and cognitive abilities. Conversely, altered activity during development actively contributes to adult miswiring relevant for disease conditions, instead of simply reflecting pathological maturation.