Key role of 5-HT1A receptors in the modulation of the neuronal network underlying the respiratory rhythm generation in lampreys

In mammals, 5‐HTexcitatory respiratory effects imply 5‐HT1A receptor‐mediated disinhibition of preBötzinger complex neurons. In the lamprey, 5‐HT1A receptors are involved in the neural control of locomotion, but their role in the respiratory regulation, particularly at the level of the putative respiratory rhythm generator, the paratrigeminal respiratory group (pTRG), is not known. We hereinvestigatethe respiratory function of inhibitory 5‐HT1A receptorswithin the pTRG of theisolatedbrainstem of the adult lamprey. The 5‐HT1A receptor agonists either bath applied or microinjected into the pTRG did not cause significant effects. However, the selective 5‐HT1A receptor antagonist (S)‐WAY 100135bath applied or microinjected into the pTRG induced depressing respiratory effects or even apnea, thus revealing that 5‐HT exerts a 5‐HT1A receptor‐mediated potent tonic influence on respiration and contributes to maintain baseline levels ofrespiratory activity. Microinjections of strychnine or bicuculline, either alone or in combination, into the pTRGprevented (S)‐WAY 100135‐induced apnea. In addition, immunohistochemical studies corroborate the present findings suggestingthat 5‐HT1A receptors are widely expressed in close apposition to the soma of glycine‐immunoreactive cells located within the pTRG region. The results show that in the lamprey respiratory network 5‐HT exerts a tonic influence on respiration by a potent inhibitory control on both GABAergic and glycinergic mechanisms. The observed disinhibitory effects resemble the excitatory respiratory modulation exerted by 5‐HT1A receptor‐mediated inhibition of glycinergic and/or GABAergic neuronspresent in mammals,supporting the notion that some features of the neuronal network subserving respiratory rhythm generation are highly conserved throughout phylogeny.