Sleep Shapes Brain Complexity and Cognition in Early Development

Objective

We know very little about developmental sleep. It has been suggested that chronic bad sleep in young animals can impair cortical architectures, causing dysfunctional cognitive development. Coherently, sleep deprivation in early life prevents synaptic pruning in postnatal brain maturation. We hypothesize that sleep is necessary to correctly shape and differentiate healthy brain circuits during the development of sensory- motor functionalities in postnatal maturation. We argue that incorrect wiring may lead to aberrant multisensory and motor integration with the emergence of neurodevelopmental cognitive disorders. To test this, we will systematically track differentiation of large-scale brain circuits by computing the Perturbational Complexity Index (PCI) in rats, from infancy (P9) to adulthood (P45). PCI probes the degree of integration and differentiation of evoked potentials, triggered by cortical electrical stimulation and measured by 32 channels EEG and LFP. We expect a gradual PCI increase along development, until adulthood, due to progressive differentiation of the highly integrated thalamic-cortical network. The gradual increment of brain complexity should correlate with network refinement at local-scale and maturation of inhibitory circuits. At the same time, PCI increase should correlate with cognitive maturation, which will be measured as behavioral performance in Y maze task, along development. We will use DREADD technique to selectively activate the awake promoter lateral hypothalamus and ventral tegmental area during sleep, along development, introducing chronic sleep alterations. We expect that rats with postnatal sleep disturbance will show reduced PCI due to impaired network differentiation, affecting cognition. This project will provide the still missing causal link across disturbed postnatal sleep, impaired maturation of brain circuits and dysfunctional cognitive development. This study might also suggest PCI as novel biomarkers for early diagnosis.