Apnea Alters the Pattern of Intermittent Hypoxia‐Induced Long Term Facilitation in Anesthetized Mice

Abstract

Intermittent hypoxia (IH) can trigger persistent increases in efferent hypoglossal (XII) motor output (i.e. long‐term facilitation, LTF) in several species, but this response has not been investigated in the mouse. As a prelude to studies in genetic “knockout” mice, our first objective was to determine if the pattern of XII LTF evoked by IH in anesthetized 129SVE mice was similar to that reported in other species. Our second purpose was to test the hypothesis that the expression of XII LTF would be altered if IH was preceded by a period of apnea‐induced XII inactivity. Mice were anesthetized with urethane, tracheotomized and vagotomized, and XII nerve activity was recorded bilaterally. A “time control” group (N=4) showed no changes in efferent XII output over a 90 min recording period with PETCO2 maintained constant at or near 35 mmHg. In another group (N=6), baseline was followed by IH (3 × 1 min hypoxia, 10%O2, separated by 3 min of hyperoxia, 50% O2). These mice showed robust facilitation, but surprisingly this was evident immediately following the final bout of hypoxia. In contrast, mice that experienced a brief (~ 3 min) period of apnea (N=4) before IH showed a gradual increase in XII bursting over the 90 min post‐IH period. These preliminary results indicate that IH triggers robust XII LTF in urethane anesthetized mice, and a brief period of apnea can alter the pattern of LTF expression.Funding: Parker B. Francis Fellowship (MKE), 2R01HD052682–06A1 (DDF), Craig H. Neilsen Foundation #220521 (MSS)