Neuronal mechanisms of respiratory rhythm generation: An approach using in vitro preparation

The respiratory network in the ventrolateral medulla of the brainstem-spinal cord preparation from newborn rat involves pre-inspiratory (Pre-I) neurons, three types of inspiratory (Insp I, II, III) neurons and two types of expiratory (Exp-i, Exp-p-i) neurons as major subtypes, which were classified according to patterns of postsynaptic potentials. The neuronal respiratory-related membrane potential fluctuations of these cells indicate at least four distinguishable phases of the in vitro respiratory cycle: pre-inspiratory, inspiratory, post-inspiratory (E1), and late-expiratory (E2). A current hypothesis for the central pattern generator of respiration proposed by our group is that Pre-I neurons in the rostral ventrolateral medulla, with intrinsic burster properties, produce the primary respiration rhythm. This rhythm triggers an inspiratory pattern generator composed of Insp neurons in the rostral and caudal ventrolateral medulla. Respiratory neurons possess several types of ionic channels which are involved in the generation of rhythm and burst pattern. Particularly P-type Ca2+ channels and TTX-sensitive persistent Na+ channels are postulated to contribute to the intrinsic burst generation of Pre-I neurons. N-type Ca2+ channels may be involved in the maintenance and termination of inspiratory burst activity via the activation of Ca2+-dependent K+ channels. Respiratory neuron networks in this preparation were compared with those of different in vitro preparations, like rhythmic slices or perfused brainstems and of adult mammals in vivo. Many types of synaptic connections among respiratory neurons in adult mammals were also found in the (rostral) ventrolateral medulla of a brainstem-spinal cord preparation from newborn rat. The characteristics of the inspiratory burst pattern and inspiratory off-switch mechanisms in newborn rat preparations might be explained by insufficient inhibitory (or excitatory) synaptic inputs to the inspiratory pattern generator due to an immature neuron network and/or deafferentiation.