Effects of adverse neonatal experience on cortical subplate neurons

The early repetitive pain and maternal separation related to preterm birth are associated with a high incidence of cognitive and behavioral defects, indicating disruption of microcircuitry in the principal brain region implicated in complex neural processing, the cortex. During the precise time period when most preterm children are born, the cortex is involved in massive organizational strategies in which neurons of the developmental subplate play many fundamental roles. The major goal of the proposed experiments is to test the hypothesis that adverse neonatal experiences associated with preterm birth affect this crucial subset of neurons. Because rats exposed to repetitive neonatal pain develop deficits mimicking the outcomes of ex-preterm children, we propose to characterize subplate neurons in the developing cortex of rodents that have undergone adverse perinatal experiences. Utilizing cellular labeling techniques, and correlated light and fluorescent microscopy, we will compare the numbers, distribution and processes of subplate neurons between treated and control animals during development, and again at maturity. We hypothesize that following adverse perinatal experiences, we will find disturbances in abundance, position and/or connective patterns of subplate neurons, thus identifying a mechanism whereby normal development of the mammalian cortex may be disrupted. Using these data, we will begin to predict how disruption of subplate neurons may be implicated in the developmental disorders associated with ex-preterm children.

It is expected that this research will provide Dr. Clancy with sufficient training in pain protocols, neurolabeling techniques, and analysis of apoptosis, to transfer similar studies to her home institution where a great number of undergraduate research students, vital to the long range success of this project, are enrolled. It is also expected that the research will support development of proposals for federal funds to continue to investigate in detail how disruption of the cortex may be evidenced in developmental disorders, especially as associated with perinatal pain. Because the project effectively pairs the expertise and research goals of both Dr. Clancy and Dr. Anand, it is also expected that collaboration between the labs will continue.