Temporal Organization of Spontaneous Movement in Fetal Mice across Uterine Environmental Conditions using Direct Observational Techniques and High Resolution Ultrasound Imaging

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Prenatal insult to the developing nervous system is one of the leading causes of developmental disabilities such as cerebral palsy, autism, or mental retardation. Current animal models of prenatal neural insult hold promise for the development of assessment tools for these disorders, using methods of direct observation of the rodent fetus and detailed quantification of limb movements. Despite this promise, the environment of the rodent fetus under direct observation is not equivalent to that of the human fetus typically observed with ultrasound. Additionally, current methods using ultrasound to observe the rodent fetus in utero greatly impact the behavior of the fetal subject, particularly when general anesthesia is used. In order to determine how these changes in observational condition and prenatal environment impact spontaneous movement of the fetus, pregnant C57BL/6J mice were prepared with spinal anesthesia for fetal observation free from general anesthesia. On the day before birth, a single fetus from each pregnancy was observed under one of three environmental or observational conditions: (a) simultaneous direct observation and ultrasound imaging, in order to compare these two observational techniques, (b) ultrasound visualization of the fetus under uterine externalization, in order to assess the impact of the uterine environment on movement visible with sonography and (c) intra-abdominal ultrasound observation of fetal movement, creating a translational model more equivalent to methods used with the human fetus. Ultrasound was collected using a 40 MHz transducer probe and VisualSonics Vevo 770 system. Movement was scored from play back of DV recordings, and analyzed with a measure called Interlimb Movement Synchrony, which quantifies the temporal patterning between limb pairs. This measure has been observed to produce clear developmental patterns in a number of species, including preterm human infants, and has been found sensitive in detecting prenatal toxin exposure in fetal rats. Analysis of the direct and ultrasound observations revealed no differences in synchrony profiles, with a mean kappa adjusted reliability of 85%. Although lower rates of movement were observed in both the externalized uterine and intra-abdominal conditions, only minor differences in Interlimb Synchrony profiles were observed. Taken together these results suggest the observational techniques employing direct and ultrasound observations hold promise as tools in developing and assessing translational models of human fetal neural functioning and developmental disabilities.


Abstract of poster presented at the 38th Annual Meeting of the Society for Neuroscience, Washington, DC, November 15-19, 2008.