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DSCAM deficiency causes loss of pre-inspiratory neuron synchroneity and perinatal death
Kenji Amano1, Morimitsu Fujii, Satoru Arata
1Laboratory for Neurogenetics, RIKEN Brain Science Institute, Wako-shi, Saitama 351-0198, Japan.
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.
Insights
Down syndrome cell adhesion molecule (DSCAM) is vital for respiratory control. Its absence in mice caused severe breathing defects and early death, highlighting DSCAM's critical role in neural regulation.
Area of Science:
- Neuroscience
- Developmental Biology
- Physiology
Background:
- Down syndrome cell adhesion molecule (DSCAM) is a crucial neural adhesion molecule involved in neural development.
- Its precise role in central respiratory regulation remains largely uncharacterized.
Purpose of the Study:
- To investigate the function of DSCAM in central respiratory regulation.
- To determine the consequences of DSCAM disruption on respiratory control in vivo and in vitro.
Main Methods:
- Generation of Dscam null mutant mice (Dscam(-/-)) and heterozygous mice (Dscam(+/-)).
- Whole-body plethysmography to assess respiratory function.
- Ex vivo medulla-spinal cord preparation with optical imaging using voltage-sensitive dye to analyze neural activity.
Main Results:
- Dscam(-/-) mice exhibited irregular respiration, reduced response to hypercapnia, and died within 24 hours post-birth.
- Ex vivo preparations showed disrupted rhythm generation and loss of synchrony in respiratory neurons in Dscam(-/-) mice.
- Dscam(+/-) mice displayed milder respiratory irregularities, suggesting a dosage-dependent effect.
Conclusions:
- DSCAM is essential for normal central respiratory regulation.
- Disruption of DSCAM leads to severe respiratory dysfunction and impacts neural circuit synchrony.
- DSCAM's role in respiration is dosage-dependent, with implications for understanding neural development and respiratory disorders.
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