Grant: Discovery Grants Program - Individual

Respiration is a vital motor behaviour that begins at birth and is maintained throughout life. The neural mechanisms generating and modulating respiration are still not well understood. Such an understanding requires knowledge relative to the synaptic connectivity of the entire network as well as the membrane properties of the comprising generator neurons. The complexity of the mammalian Central Nervous System (CNS) renders this task difficult and simpler CNS models are needed. Lampreys are basal vertebrates that have diverged from other vertebrate species some 560 million years ago. The organisation of their brainstem, however, is strikingly similar to that of mammals. Moreover, the neural circuitry generating respiration in lampreys 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 to respiration will be established as well as the connectivity in the respiratory network.The respiratory rhythm is modulated under many circumstances. For instance, respiration increases in association with movement. This has traditionally been attributed to a chemoreceptive feedback. However, we have recently shown that a central feed-forward mechanism is involved with direct connections between a locomotor control centre in the midbrain and the respiratory generating area in the hindbrain. We propose to identify the details of the cellular mechanisms involved in this feed-forward circuitry. Taken together the information gained from this research should provide testable hypotheses on the neural organization responsible for the generation and modulation of respiration in mammals, including humans.