Substance P, a peptidergic modulator, also plays a role in neuromodulation of the pre-BötC. It is often coreleased with other neurotransmitters. Substance P activates the inspiratory frequency at the level of the network and behavioral systems. Cellularly, substance P is involved in the depolarization of nonpacemaker neurons slowly, causing an increase in action potential firing rate. The neuropeptide can also activate CS pacemakers and less dramatically, CI pacemakers. This leads to an increase in burst amplitude, frequency, and duration. When Substance P is coreleased with serotonin, it plays a crucial role in hypoxic response. This occurs because substance P stabilizes the respiratory rhythm through depolarization of neurons and activation of Pacemaker neurons.