Cellular mechanisms underlying modulation of breathing pattern in mammals.

Understanding the generation and modulation of respiratory pattern requires knowledge of the cellular and network properties of the central nervous system controller. Although considerable efforts have focused on network properties, recent efforts in several laboratories have emphasized the importance of cellular mechanisms. Using a novel experimental in vitro system, we have been able to investigate several classes of cellular mechanisms difficult or impossible to study in vivo or in tissue slices. The conclusions and hypotheses that we have made include the following: 1. Respiratory rhythm and spatiotemporal patterns of (pre)motoneuronal activity are separately generated. 2. Cl- -dependent inhibition is critical in burst pattern formation. 3. Cl- -dependent and at least one type of K+-dependent (GABAB) inhibition is not necessary for rhythm generation. 4. Inhibitory neurotransmitters, including those acting through second messenger systems, can modulate respiratory rhythm and pattern. 5. Pacemakers underlie rhythm generation. 6. Excitatory inspiratory drive to respiratory motoneurons is mediated by an excitatory amino acid, which acts on both post- and presynaptic receptors. The effort to verify these conclusions and test these hypotheses should greatly enhance our understanding of the nervous control of respiration.