Upregulation of norepinephrine (NE) causes instability of respiratory rhythm under acute intermitted hypoxia (AIH) at in vivo whole mice

Abstract

We already reported that norepinephrine (NE) stabilizes the respiratory rhythm generation in the pre-Bötzinger complex (pre-BötC). However, under the application of NE, further manipulation of acute intermitted hypoxia (AIH) presents irregularity of respiratory related population activity at slice preparation. In this study, therefore, we show that direct injection of NE for the pre-BötC following AIH can replicate the instability of real respiratory rhythm at in vivo whole p15–23 mice. The respiratory activity was detected by EMG recordings on intercostal muscle. Compare to normal AIH condition without injection of NE for the pre-BötC, NE injection plus AIH had the irregularity of respiratory frequency. Glutamate injection for locus ceruleus following AIH also reproduced the instability of the respiratory frequency. For the respiratory instability, pre-injection of strychnine (STR, glycine receptor's blocker) under NE plus AIH restored the instability of the respiratory rhythm. But, post-injection of the STR did not recover the rhythm. These results suggest that release of NE is linking to activation of inhibitory components (presynaptic glycine release and/or postsynaptic glycine receptors). Further studies are underway about recovering mechanisms of STR and relationship between inhibitory component and release of NE in the pre-BötC.