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Pretreatment with Ampakine CX717 Enhances Long‐Term Facilitation (LTF) of Inspiratory Hypoglossal (XII) Bursting, But Only When Initial Burst Output is Low
Author(s) -
Turner Sara,
Elmallah Mai,
Hoyt Aaron,
Greer John,
Fuller David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.986.3
Subject(s) - bursting , respiratory system , long term potentiation , anesthesia , ampa receptor , phrenic nerve , chemistry , excitatory postsynaptic potential , neurotransmission , medicine , neuroscience , glutamate receptor , receptor , psychology
Glutamatergic synaptic transmission is a fundamental component of the neural drive to breathe, and AMPA‐mediated synaptic currents contribute to respiratory rhythmogenesis and respiratory motoneuron depolarization during inspiration. Ampakines are positive allosteric modulators of AMPA receptors, and have been shown to potentiate neuroplasticity in models of long‐term potentiation. The aim of this study was to explore the impact of ampakine CX717 on intermittent‐hypoxia (IH) induced respiratory LTF in urethane anesthetized, vagotomized, and mechanically ventilated adult mice. Ampakine was administered at 15 mg/kg (intraperitoneal injection) 10‐min prior to 3, 1‐min bouts of hypoxia (10% O 2 ). Initial control experiments indicated that a single 15 mg/kg ampakine injection had no persistent impact on XII motor output in this preparation. However, pairing ampakine with IH resulted in enhanced LTF. Thus, over a 90‐min period following IH, the amplitude of the XII inspiratory burst was significantly higher in mice pretreated with ampakine (485 ± 96% of baseline) vs. sham‐injected mice (198 ± 32% of baseline; 2 way repeated measure ANOVA, P<0.05). In addition, the absolute value of the initial pre‐IH baseline XII inspiratory burst amplitude (i.e., raw voltage or “arbitrary units”) was robustly correlated (P<0.001) with the magnitude of LTF (%baseline). Thus, the probability of the ampakine injection evoking a greater LTF was much greater when baseline outputs were low. A similar relationship was not detectable in the non‐ampakine treated mice (P=0.852). We conclude that IH‐induced respiratory LTF can be enhanced by pre‐treatment with ampakine, but the drug is not effective when initial respiratory output is high. These data suggest that ampakines have potential to enhance the impact IH as a neurorehabilitation modality for neurologic conditions associated with reduced respiratory motor output. Support or Funding Information 1 R01 NS080180‐01A1 (DDF), State of Florida Brain and Spinal Cord Injury Research Program (DDF), Canadian Institutes for Health Research (JJG), Craig H. Neilsen Foundation 313369 (SMFT)