Methods for in vivo behavioral observation of the mouse fetus

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DESCRIPTION (provided by applicant): Prenatal damage to the developing nervous system is one of the leading causes of developmental disabilities in children. The outcome of this early neural damage is typically a disorder such as cerebral palsy, autism, or mental retardation. Often these disabilities are not diagnosed until the 2nd or 3rd year of life, delaying much needed interventions and therapy during this critical early period of development. Delays in diagnosis may occur because little is known about the immediate changes in functional development that transpire between the time of neural insult and the emergence of obvious dysfunction. Because motor deficits are the hallmark of many developmental disorders, the ontogeny of early motor dysfunction may be paramount to understanding the origins of these disorders. More importantly, if early indicators of movement dysfunction could be identified, therapy or treatment could be started early when it would be most beneficial. Current animal models of prenatal neural insult hold promise for the development of such assessments. Using methods which allow direct in vivo observation of the rat or mouse fetus, detailed quantification of spontaneous limb movements and deficits in inter-limb coordination are possible. However, the environment of the rodent fetus under direct observation is not equivalent to that of the human fetus while observed through ultrasound, and methods using ultrasound to observe the rodent fetus in utero greatly impact the behavior of the fetal subject. To overcome these obstacles, we will develop an innovative use of high resolution ultrasound for behavioral observation of the mouse fetus, by combining this new technology with methods permitting direct observation of the fetal rodent. The successful integration of these two methods will break new ground, advancing the study of developmental disabilities through noninvasive observation of fetal behavior in animal models. We envision that these studies will lead to a new area of investigation in prenatal behavioral development, which will utilize transgenic mice, environmental insults, and ultrasound observation of fetal behavior to create prenatal mouse models of early developmental disabilities. PUBLIC HEALTH RELEVANCE STATEMENT The new methodology outlined in this proposal will create a necessary bridge between animal and human models, allowing similar comparisons of fetal behavior. These new methods will also lay a foundation for the development of new diagnostic tests to detect developmental disabilities in the human fetus. Ultimately, the application of these methods will increase our knowledge about developmental disabilities that will allow their prevention, prenatal detection, and cure.