NTS Phox2b Neurons in Chemosensory Processing and Interoceptive Pathways
Congenital Central Hypoventilation Syndrome (CCHS) is a rare disorder caused by mutations in the Phox2b gene, which disrupts the brain’s ability to control breathing, especially during sleep. People with CCHS often experience life-threatening pauses in breathing, low oxygen levels, and other breathing difficulties. While research has highlighted the role of Phox2b in the retrotrapezoid nucleus (RTN), findings suggest the RTN alone cannot fully explain this condition. Emerging evidence indicates that the nucleus of the solitary tract (NTS), another brainstem center that contains Phox2b neurons, plays a critical role in regulating breathing by processing signals from the body and the brain. Our recent studies revealed that NTS neurons comprise diverse subsets, each playing distinct roles in regulating breathing behaviors, such as responding to low oxygen or other breathing challenges. This project aims to uncover how NTS Phox2b neurons work and how they receive signals to control breathing. Our findings could lead to better understanding and new treatments for CCHS and related breathing disorders.
$75,000/1 year
Determination of Medullary Neurons Underlying Congenital Hypoventilation
Luis R. Hernandez-Miranda and Ulf Strauss team up to investigate the functional relevance of a molecularly defined neuron type (called dB2) in congenital central hypoventilation syndrome (CCHS).
CCHS (Congenital Central Hypoventilation Syndrome) is a rare but serious breathing disorder that is usually diagnosed in newborns. Babies with this condition have difficulty breathing properly, especially during sleep, because their bodies don’t respond well to changes in oxygen or carbon dioxide levels. This happens because the brain’s breathing control centers don’t work as they should.
The condition is linked to mutations in two important genes, PHOX2B and LBX1, but we still don’t fully understand which specific brain neurons are affected by these mutations. Recent research has identified a group of brain cells called dB2 neurons in a part of the brain responsible for controlling breathing. These neurons co-express both PHOX2B and LBX1. When PHOX2B or LBX1 genes are mutated, these neurons change in ways that might explain the breathing problems seen in CCHS, according to studies in mice. However, we don’t yet know exactly how these neurons connect to the larger breathing control system in the brain.
This project aims to learn more about what makes dB2 neurons unique, how they work within the breathing control system, and how the PHOX2B and LBX1 genes influence their development and function.
$75,000/1 year