This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The adverse experiences related to preterm birth are associated with cognitive and behavioral defects in ex-preterm children, indicating disruption of the cortex, the primary brain region involved in aptitude and intelligence. Nevertheless, it has not been established that premature infants experience pain or neural consequences from pain, nor is it known if the benefits of anesthetic drugs outweigh disadvantages in this age group. The overall goals of this project are to understand how pain and/or anesthesia in newborns affects the manner in which brain architecture develops, matures, and ages, with a focus on the cortex, and the role of group of a cells critically involved in normal cortical development, the subplate neurons. We hypothesize that when perinatal mammals are exposed to repetitive pain or prolonged anesthesia, cortical organization is irreparably altered, a disruption that can be minimized if anesthesia is administered for an appropriate time period. Because rats exposed to repetitive neonatal pain and/or anesthesia develop deficits mimicking those of ex-preterm children, we propose to characterize the cortex of rodents that have undergone adverse perinatal experiences with and without anesthetic drugs. Utilizing cellular labeling techniques, and correlated light and fluorescent microscopy, we will compare the structure of the cortex, including subplate neurons, between treated and control animals across development. Using bioinfomatic techniques, we will generate predictions for appropriate anesthetic intervals in experimental animals. Using these data, we will begin to understand how cortical disruption may be implicated in developmental disorders associated with ex-preterm children. It is expected that this research will demonstrate to students the potential of careers in biomedical research, as well as support federal funding for undergraduate research experiences, and ultimately lead to the development of proposals for federal funds to continue to investigate in detail how disruption of the cortex may be evidenced in developmental disord
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