Alcohol in Neocortex Development and Plasticity

点击翻译按钮获取中文摘要

Abstract Children with fetal alcohol spectrum disorders (FASD) often present sensory alterations such as aversion to multiple sensory stimuli presented at the same time, attention deficits, poor visual-motor integration, and disrupted general sensory processing. There is growing evidence supporting the idea that these problems give rise to social problems and learning deficits. Therefore, understanding the effects of developmental alcohol exposure in the processing of different sensory modalities is crucial to devise interventions to ameliorate neurobehavioral problems seen in FASD. Multisensory integration (MSI) is a higher order function in which the combination of inputs from two or more sensory modalities leads to either facilitation or suppression of neuronal responses. MSI relies on the precise wiring of the individual sensory systems and then on the accuracy of convergence of these systems to multisensory processing areas. This precision is acquired by activity-dependent neuronal plasticity processes that include sprouting and pruning of connections. In the human cortex, most of these plastic changes occur during the third trimester of human gestation. Ethanol is known to severely affect activity-dependent neuronal plasticity in the cortex. Our overarching hypothesis is that alcohol exposure during development disrupts the functional and structural connectivity of multisensory cortical areas altering MSI and contributing to neurobehavioral impairments in FASD. In the studies proposed here we will use a combination of advanced imaging techniques; in vivo electrophysiology and a novel ex vivo slice preparation to evaluate the effect of developmental alcohol exposure on the structural, functional and electrophysiological properties of multisensory cortical areas. Moreover we will test whether boosting activity-dependent neuronal plasticity would reverse the effects of alcohol on multisensory processing. The accomplishment of these experiments will make a major and paradigm-shifting contribution towards the FASD research field.