DSCAM Deficiency Causes Loss of Pre-Inspiratory Neuron Synchroneity and Perinatal Death
Open Access
- 4 March 2009
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 29 (9), 2984-2996
- https://doi.org/10.1523/jneurosci.3624-08.2009
Abstract
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 h after birth. Whole-body plethysmography showed irregular respiration and lower ventilatory response to hypercapnia in the null mutants. Furthermore, 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 neurons located in the rostral ventrolateral medulla 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.Keywords
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