Ileana L. Hanganu-Opatz
Developmental Neurophysiology, Center of Molecular Neurobiology, University Medical Center Hamburg-Eppendorf
Binding of neuronal assemblies by synchronizing their activity patterns in oscillatory rhythms enables sensory perception, attention and memory. The ability to generate oscillatory rhythms is not a hallmark of the adult brain, but is present already during early development. Synchronized patterns of oscillatory activity are present in the sensory (visual, somatosensory) cortical areas of both premature infants and neonatal rodents and are triggered by endogenous activation of sensory periphery and intracortical activation. They appear to act as a template facilitating the establishment of cortical maps, which are requested for sensory processing, and to control the early multisensory integration. Whether such oscillatory activity interferes with the maturation of neuronal networks underlying the cognitive performance remains unknown. Combining in vivo electrophysiology and pharmacology with immunohistochemistry and behavioral testing we identified and characterized for the first time the patterns of oscillatory activity in the developing rat prefrontal cortex (PFC) and unraveled their mechanisms of generation within a prefrontal-hippocampal-subcortical circuit. Bursts of oscillatory activity with characteristic temporal and spatial organization synchronize in theta-gamma frequency band the neonatal PFC. They result from the activation of local prefrontal networks driven by hippocampal theta bursts via direct synaptic projections. Tight oscillatory coupling emerges also between the neonatal hippocampus and entorhinal cortex. This early prefrontal-hippocampal-entorhinal network is subject of intense cholinergic modulation in relationship with the early behavioral development. Miswiring within the developing prefrontal-hippocampal-subcortical network due to abnormal patterns of early activity and synchronization may account for specific impairment of cognitive abilities that has been reported for several neurodevelopmental disorders, such as neonatal ischemia and schizophrenia.