The effects of substance P, bradykinin, and histamine on inspiratory neurons of the preBötC within a brainstem slice preparation. (A) Electrophysiology traces are shown in pairs from the preBötC population (∫, upper trace in each case) and a single inspiratory neuron of the preBötC (lower trace in each case) during synaptic isolation, without modulation, and in response to substance P (SP; 1 μM), bradykinin (Br; 10 μM), and histamine (H; 10 μM). (Top) Neuron 2 is silent in the absence of exogenous neuromodulation, is stimulated in the presence of substance P to exhibit a tonic firing pattern, is silent in the presence of bradykinin, and was not tested in the presence of histamine. (Middle) Neuron 10 is tonic in the absence of exogenous neuromodulation. Although both substance P and bradykinin stimulate a tonic firing rate, histamine changes the tonic firing pattern to a burster phenotype. (Bottom) Neuron 13 exhibits a burster phenotype in the absence of exogenous neuromodulation. Substance P stimulates the burster phenotype, whereas both bradykinin and histamine caused Neuron 13 to depolarize (>1.5 mV), requiring the injection of a hyperpolarizing current to prevent depolarization block. [Scale bars: 1 s (x-axis) and 20 mV (y-axis).] (B–D) Summaries of isolated inspiratory neurons (n = 18). These summaries demonstrate the diverse effects of substance P, bradykinin, and histamine on synaptically isolated inspiratory neurons. Examples of silent, tonic, and burster firing patterns are shown in A. (B) Firing pattern. (C) Change in firing rate. (D) Comparison of bradykinin responses as a ratio of substance P responses from individual substance P-sensitive dissociated cells (Left) and inspiratory preBötC neurons within the brainstem slice preparation (Right).