TY - JOUR T1 - Intermittent Hypoxia Enhances Functional Connectivity of Mid-Cervical Spinal Interneurons JF - The Journal of Neuroscience JO - J. Neurosci. DO - 10.1523/JNEUROSCI.0992-17.2017 SP - 0992-17 AU - K.A. Streeter AU - M.D. Sunshine AU - S. Patel AU - E.J. Gonzalez-Rothi AU - P.J. Reier AU - D.M. Baekey AU - D.D. Fuller Y1 - 2017/07/27 UR - http://www.jneurosci.org/content/early/2017/07/27/JNEUROSCI.0992-17.2017.abstract N2 - Brief, intermittent oxygen reductions (acute intermittent hypoxia, AIH) evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most mid-cervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multi-electrode array was used to record C4/5 spinal discharge before (baseline, BL), during, and 15 min after 3, 5-min hypoxic episodes (11% O2, H1-H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared to BL (19%; p<0.0001). Another subset had a similar response following each episode (40%) compared to BL (19%; p<0.0001). In the latter group, connectivity remained elevated 15 min post-AIH (30%; p=0.0002). Inhibitory C-IN connectivity increased during H1-H3 (4.5%, p=0.0160), but was reduced 15 min post-AIH (0.5%; p=0.0439). Spike-triggered averaging indicated that a subset of C-INs is synaptically coupled to phrenic motoneurons and excitatory inputs to these “pre-phrenic” cells increased during AIH. We conclude that AIH alters connectivity of the mid-cervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network.SIGNIFICANCE STATEMENTAcute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH. ER -