Gasping ActivityIn Vitro: A Rhythm Dependent on 5-HT2AReceptors

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Abstract
Many rhythmic behaviors are continuously modulated by endogenous peptides and amines, but whether neuromodulation is critical to the expression of a rhythmic behavior often remains unknown, particularly in mammals. Here, we address this issue in the respiratory network that was isolated in spontaneously rhythmic medullary slice preparations from mice. Under control conditions, the respiratory network generates fictive eupneic activity. We hypothesized previously that this activity depends on two types of pacemaker neurons. The bursting properties of one pacemaker rely on the persistent sodium current (INa(p)) and are insensitive to blockade of calcium channels with cadmium (CI-pacemakers), whereas bursting mechanisms of a second pacemaker are sensitive to cadmium (CS-pacemakers) and the calcium-dependent nonspecific cation current blocker flufenamic acid. During hypoxia, fictive eupneic activity is supplanted by the neural correlate of gasping, which is proposed to depend only on CI-pacemakers. Because CI-pacemakers require endogenous activation of 5-HT2Areceptors, we tested the hypothesis that 5-HT2Areceptor activation is critical for gasping. Here, we demonstrate that fictive gasping and CI-pacemaker bursting were selectively eliminated by the 5-HT2Areceptor antagonist piperidine or ketanserin. Neither 5-HT2Aantagonist eliminated bursting by CS-pacemakers and ventral respiratory group (VRG) population activity. However, this VRG activity was very different from eupneic activity. In the presence of 5-HT2Aantagonists, VRG activity was eliminated by flufenamic acid and could not be reliably restored by adding substance P. These data support the hypothesis that two types of pacemaker bursting mechanisms underlie fictive eupnea, whereas only one burst mechanism is critical for gasping.