Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control.  However, molecular mechanisms that control their activity and responsiveness to neurotransmitters are completely unknown.  To make this determination, we use a combination of in vitro (splice-patch recording) and in vivo (plethysmography) recording techniques in conjunction with genetic approaches to examine chemoreceptor function at the cellular and systems levels. This combination of approaches will identify key determinants of chemoreceptor activity and in doing so identify new therapeutic avenues for the treatment of respiratory control disorders.