| The respiratory rhythm is generated within the brainstem by a neuronal network located in the ventral respiratory group (VRG). Isolated in a transverse brainstem slice preparation, the VRG including the pre-Boetzinger complex (PBC) still generates rhythmic activity, which can be recorded in the VRG and in the hypoglossal motor nucleus (XII). Under normoxic conditions, two respiratory patterns were expressed: eupneic and sigh bursts. Intracellular recordings revealed, that fine-tuned synaptic transmission and intrinsic properties of respiratory neurons are important for establishing the pattern of eupneic activity and modulating respiratory frequencies.; Anoxic conditions and the neuromodulator substance P (SP) lead to a differential modulation of the XII and the VRG. An increase in eupneic burst amplitudes occurred only in the XII but not in the VRG. Respiratory frequencies, in contrast, were modulated simultaneously in the VRG and in the XII. Both anoxia and substance P lead to a stronger frequency increase in sigh bursts compared to eupneic bursts.; Underlying cellular mechanisms of the modulations by substance P revealed the following effects. (1) SP decreased potassium currents and (2) caused a presynaptic inhibition of excitatory and inhibitory synaptic neurotransmission. (3) Embedded in the network, SP caused an excitation, which was reflected in an increase of the number of excitatory and inhibitory postsynaptic currents and in the concurrent expression of an inward current. (4) A transient decrease in high-voltage activated (HVA) calcium currents occurred only in a subgroup of cells.; To determine the importance of SP in respiration, basal respiration and the anoxic response were compared in absence and presence of substance P using the SP-antagonist spantide and pre-protachykinin A (PPT-A) mutant mice, which lack substance P. Although fictive respiratory activity was still generated spontaneously in the absence of substance P, the respiratory rhythm was irregular and the gain of the anoxic response was increased. Elevated concentrations of substance P, in contrast, decreased the gain of the anoxic augmentation, indicating the importance of substance P in the maintenance and stability of regular breathing frequencies. |
