Loss of Pre-Inspiratory Neuron Synchroneity in Mice with DSCAM Deficiency
Down syndrome cell adhesion molecule (DSCAM) is a neural adhesion molecule that plays diverse roles in neural development. We disrupted the Dscam locus in mice and found that the null mutants (Dscam -/-) died within 24 hours after birth. Whole body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Further, a medulla-spinal cord preparation of Dscam -/- mice showed that the C4 ventral root activity, which drives diaphragm contraction for inspiration, had an irregular rhythm with frequent apneas. Optical imaging of the preparation using voltage-sensitive dye revealed that the pre-inspiratory (Pre-I) neurons located in the rostral ventrolateral medulla (RVLM) and belonging to the rhythm generator for respiration, lost their synchroneity in Dscam -/- mice. Dscam +/− mice, which survived to adulthood without any overt abnormalities, also showed irregular respiration but milder than Dscam -/- mice. These results suggest that DSCAM plays a critical role in central respiratory regulation in a dosage-dependent manner. These results have been published (Amano et al. 2009).
KeywordsDown Syndrome Facial Nerve Activity Facial Nucleus Rostral Ventrolateral Medulla Ventral Medulla
This work was partly supported by a grant from RIKEN Brain Science Institute, Grant-in-Aid for Scientific Research (KAKENHI) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We thank Dr. T. Takeuchi, N. Nishiyama, and Y. Onodera for technical support, Dr. K. Yamaguchi for helpful suggestions.
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