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Loss of pre-inspiratory neuron synchroneity in mice with DSCAM deficiency
Kenji Amano1, Morimitsu Fujii, Satoru Arata
1Laboratory for Neurogenetics, RIKEN Brain Science Institute, Saitama, Japan. kenjia@brain.riken.jp
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 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).
Insights
Down syndrome cell adhesion molecule (DSCAM) is crucial for regulating breathing. Mice lacking DSCAM exhibit severe respiratory defects and die shortly after birth, highlighting its vital role in neural development and respiratory control.
Area of Science:
- Neuroscience
- Developmental Biology
- Physiology
Background:
- Down syndrome cell adhesion molecule (DSCAM) is a key neural adhesion molecule.
- DSCAM is implicated in various aspects of neural development.
Purpose of the Study:
- To investigate the role of DSCAM in central respiratory regulation.
- To determine the consequences of DSCAM disruption on respiratory function in mice.
Main Methods:
- Generation of Dscam null mutant mice (Dscam (-/-)) and heterozygous mice (Dscam (+/-)).
- Whole body plethysmography to assess respiratory parameters.
- 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 of birth.
- Neural preparations from Dscam (-/-) mice showed disrupted rhythm generation in respiratory neurons (Pre-I neurons in RVLM) and apneas.
- Dscam (+/-) mice displayed milder respiratory irregularities, suggesting a dosage-dependent effect of DSCAM.
Conclusions:
- DSCAM is essential for normal central respiratory regulation.
- Disruption of DSCAM function leads to severe respiratory dysfunction and lethality.
- DSCAM plays a critical, dosage-dependent role in the neural control of breathing.
