Hypoxia-induced modulation of the respiratory CPG.

Despite recent advances in our understanding of the neural control of breathing, the precise cellular, synaptic, and molecular mechanisms underlying the generation and modulation of respiratory rhythm remain largely unknown. This lack of fundamental knowledge in the field of neural control of respiration is likely due to the complexity of the mammalian brain where synaptic connectivity between central respiratory neurons, motor neurons and their peripheral counterparts cannot be mapped reliably. We have therefore developed an invertebrate model system wherein the essential elements of the central pattern generator (CPG), the motor neurons and the peripheral chemosensory cells involved in respiratory control have been worked out both in vivo and in vitro. We discuss our recent identification of peripheral, hypoxia sensitive chemoreceptor elements in a sensory organ of the pulmonate freshwater pond snail Lymnaea stagnalis, which provide an excitatory drive to the respiratory CPG neuron RPeD1 via direct chemical synaptic connections. Further studies using this unique invertebrate model system may reveal highly conserved principles of CPG neuromodulation that will remain relevant to more complex mammalian systems.