Abstract
Disturbed neuronal activity in neuropsychiatric pathologies emerges during development and might cause multifold neuronal dysfunction by interfering with apoptosis, dendritic growth and synapse formation. However, how altered electrical activity early in life impacts neuronal function and behavior of adults is unknown. Here, we address this question by transiently increasing the coordinated activity of layer 2/3 pyramidal neurons in the medial prefrontal cortex of neonatal mice and monitoring long-term functional and behavioral consequences. We show that increased activity during early development causes premature maturation of pyramidal neurons and alters interneuron density. Consequently, reduced inhibitory feedback by fast-spiking interneurons and excitation/inhibition imbalance in prefrontal circuits of young adults result in weaker evoked synchronization in gamma frequency. These structural and functional changes ultimately lead to poorer mnemonic and social abilities. Thus, prefrontal activity during early development actively controls the cognitive performance of adults and might be critical for cognitive symptoms of neuropsychiatric diseases.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵# Co-first authors
While the previous version of the manuscript addressed the fundamental question whether electrical activity during early development impacts adult cortical function and ultimately behavior, the current version demonstrates how this happens. In the previous version, we concluded that altered developmental activity causes long-lasting impairments in prefrontal gamma synchrony and cognitive abilities. The new version of the manuscript shows the cascade of events caused by increased cortical activity during early development leading to cognitive impairments in young adults. Thereby this study links main concepts implicated with neuropsychological diseases (changes in early activity, altered inhibition by parvalbumin interneurons, changes in excitation/inhibition balance, impaired gamma synchrony and cognitive impairments) and brings them into a developmental perspective.