Repetitive paired stimulation of nasotrigeminal and peripheral chemoreceptor afferents cause progressive potentiation of the diving bradycardia

Rozloznik M, Paton JF, Dutschmann M. Repetitive paired stimulation of nasotrigeminal and peripheral chemoreceptor afferents cause progressive potentiation of the diving bradycardia. Am J Physiol Regul Integr Comp Physiol 296: R80-R87, 2009. First published November 5, 2008; doi:10.1152/ajpregu.00806.2007.- Hallmarks of the mammalian diving response are protective apnea and bradycardia. These cardiorespiratory adaptations can be mimicked by stimulation of the trigeminal ethmoidal nerve (EN5) and reflect oxygen-conserving mechanisms during breath-hold dives. Increasing drive from peripheral chemoreceptors during sustained dives was reported to enhance the diving bradycardia. The underlying neuronal mechanisms, however, are unknown. In the present study, expression and plasticity of EN5-bradycardias after paired stimulation of the EN5 and peripheral chemoreceptors was investigated in the in situ working heart-brain stem preparation. Paired stimulations enhanced significantly the bradycardic responses compared with EN5-evoked bradycardia using submaximal stimulation intensity. Alternating stimulations of the EN5 followed by paired stimulation of the EN5 and chemoreceptors (10 trials, 3-min interval) caused a progressive and significant potentiation of EN5-evoked diving bradycardia. In contrast, bradycardias during paired stimulation remained unchanged during repetitive stimulation. The progressive potentiation of EN5-bradycardias was significantly enhanced after microinjection of the 5-HT3 receptor agonist (CPBG hydrochloride) into the nucleus tractus solitarii (NTS), while the 5-HT3 receptor antagonist (zacopride hydrochloride) attenuated the progressive potentiation. These results suggest an integrative function of the NTS for the multimodal mediation of the diving response. The potentiation or training of a submaximal diving bradycardia requires peripheral chemoreceptor drive and involves neurotransmission via 5-HT3 receptor within the NTS.