Neural control of respiration

点击翻译按钮获取中文摘要

Respiration is a basic rhythmic motor activity maintained throughout life. In vertebrates, it results from rhythmic activity of brainstem neurons, collectively known as “respiratory rhythm generator”. Both synaptic connectivity and membrane properties play a crucial role in generating respiration. Advances have been made in understanding the basic mechanisms underlying respiration using in vitro preparations of mammalian brainstem tissue. Because most of these in vitro preparations consist of slices of neural tissue, they do not include the entire neural circuitry responsible for respiration and its modulation. These limitations have prevented the detailed identification of the synaptic interactions between the neurons involved. We are using the lamprey, a basal vertebrate, as a powerful model to gain insight into these questions. In lampreys, respiratory activity is maintained for hours under in vitro conditions in the isolated intact brainstem and can even be maintained in semi-intact preparations that include the peripheral respiratory apparatus. The long-term objective of our research program is to characterize in detail the neural mechanisms underlying the generation and modulation of respiration. There are two distinct respiratory rhythms in lampreys: a fast (1.5 Hz) and a slow rhythm (0.02 Hz). During this next granting term, we will focus on 3 specific research themes: Theme 1 will focus on the fast respiratory rhythm. Using anatomical techniques we will define the synaptic connectivity of neurons involved in generating the fast rhythm. Whole cell patch recordings will be used to examine the contribution of excitatory and inhibitory inputs as well as the membrane properties of the neurons. Theme 2 will focus on the mechanisms responsible for generating the slow rhythm. We will use whole cell patch recordings to define the connectivity and properties of generator neurons. Because of their anatomical location in the lamprey brainstem, the groups of neurons generating the slow rhythm are excellent candidates for being the evolutionary ancestors of the neurons generating breathing in mammals. Theme 3 will focus on the mechanisms underlying the increase in respiratory activity during movement. We have discovered in lampreys a central neural substrate responsible for adapting the respiratory output to energy demands during locomotion. It consists of a feed forward mechanism from a locomotor control center to the fast respiratory rhythm generator. The lamprey model is ideal to examine such a behaviourally relevant modulation of the respiratory rhythm. We will now identify the neural mechanisms involved, focusing on the role of acetylcholine and Substance P. Altogether, we are proposing a comprehensive long-term research program to identify the mechanisms responsible for generating and modulating respiration in a basal vertebrate.