Grant: Discovery Grants Program - Individual

Respiration is a vital motor behaviour that begins at birth and is maintained throughout life. Pathological changes in breathing can have dire consequences and it is thus crucial to understand the neural mechanisms generating respiration. To do this, both the synaptic connectivity of the entire network as well as the membrane properties of the comprising generator neurons must be identified. The complexity of the mammalian Central Nervous System (CNS) renders this task difficult and we believe that the simpler CNS of lampreys could help provide a detailed understanding. In lampreys, the neural circuitry generating respiration stays active after isolation in vitro of their CNS, and continues to generate respiratory output very similar to that observed in intact animals. We propose to characterize the neural circuitry both at the system (synaptic connectivity) and cellular (intrinsic properties of neurons) levels in the CNS of lampreys. The relative contribution of synaptic and intrinsic properties in respiration will also be established. Finally, we will examine the modulation of respiration by other motor circuits in the isolated CNS. The onset of movements is accompanied by increases in the respiratory drive and previous work from our lab has revealed that the changes are pre-programmed in the CNS. We propose to identify the neural circuitry responsible for these changes. We believe that the information gained in this lower vertebrate CNS will be useful to provide testable hypotheses on the neural organization responsible for respiration in higher vertebrates, including humans.