Emergence of Visual Alertness in Cortical Networks

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DESCRIPTION (provided by applicant): Human neonates use vision to guide behavior, form caregiver attachments, and build more complex visual and cognitive abilities. Defining the mechanisms by which vision comes 'online' in time for birth is thus essential to understand the development of normal and pathological visual processing. Visual perception requires the development of organized receptive fields as well as the development of cortical states that generate visual alertness and attention. Animal models have provided a mechanistic understanding of the former, but insight into the mechanisms by which alert visual response dynamics develop has been limited by a paucity of unanesthetized animal models with demonstrated homology to fetal and perinatal human cortical activity. To overcome this limitation, my collaborators and I have made a significant investment in the characterization of a behaving infant rat model that recapitulates early human cortical activity development. We propose to use this model to identify the network mechanisms that drive the development of cortical alertness, and characterize their role in the perinatal functional maturation of the visua response. In prior studies we identified a rapid maturation of visual cortical activity occurring 23 weeks before term (birth) in humans and 1-2 days before eye opening in rats. Before this switch cortical activity is dominated by network silence, interrupted by infrequent, large amplitude oscillatory bursts that occur both spontaneously and in response to light. The electrographic signature of alertness typical of the adult waking state, namely the "activated" or "desynchronized" state in the EEG, is not observed at these ages even when the infant is clearly awake. This period ends suddenly when oscillatory bursts are replaced by fast visual responses superimposed on an activated cortical state during wakefulness, which we call "visual alertness". We will test the hypothesis the emergence of visual alertness is the result of rapid development of feed-forward cortical inhibition and a surge in norephinephrine (NE) release occurring just before eye opening. Our results will provide a novel understanding of how changing cortical network properties influence development of vision, and how ontogenetic control of the timing of these properties is achieved. We expect this information will inform the diagnosis and treatment of central visual and attention deficits prevalent in pre-term and other at risk infants.