Reductions in respiratory-related synaptic inputs to inspiratory motor neurons initiate a form of plasticity that proportionally enhances inspiratory motor output, even in the absence of changing blood gases. This form of plasticity is known as inactivity-induced inspiratory motor facilitation (iMF). iMF triggered by brief, recurrent reductions in respiratory neural activity requires local retinoic acid (RA) synthesis, but receptor subtypes activated by RA are unknown. To test the hypothesis that retinoic acid receptor alpha (RARa) is necessary for iMF, RAR subtype-specific inhibitors were delivered intrathecally above the phrenic motor pool in urethane-anesthetized, ventilated rats prior to 5, ~1min central apneas (without hypoxia; separated by 5 min) while monitoring phrenic inspiratory output. Pre-treatment with a spinal RARa inhibitor impaired the capacity for recurrent central apnea to trigger long-lasting increases in phrenic inspiratory output, but plasticity was expressed in rats pre-treated with an RAR / inhibitor. Intrathecal RA application in the absence of reduced respiratory neural activity elicited an increase in phrenic inspiratory output, which was prevented by pre-treatment with an RARa inhibitor. These data indicate that spinal RARa activation is necessary for iMF triggered by recurrent reductions in respiratory neural activity, and that RARa activation in/near the phrenic motor pool in the absence of respiratory neural activity deprivation is sufficient to elicit phrenic inspiratory motor facilitation. Understanding cellular cascades underlying plasticity induced by reductions in respiratory neural activity may define avenues for pharmacological intervention in disorders in which endogenous compensatory mechanisms that defend on-going inspiratory motor output are impaired.

中文翻译：

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维甲酸受体α激活对于复发性中枢性呼吸暂停引起的可塑性是必要和充分的

对吸气运动神经元的与呼吸相关的突触输入的减少会引发一种可塑性形式，即使在没有血气变化的情况下，也会成比例地增强吸气运动输出。这种形式的可塑性被称为不活动诱导的吸气运动促进 (iMF)。由呼吸神经活动的短暂、反复减少触发的 iMF 需要局部视黄酸 (RA) 合成，但由 RA 激活的受体亚型是未知的。为了检验视黄酸受体 α (RARa) 对 iMF 是必需的假设，RAR 亚型特异性抑制剂在 5~1 分钟中枢性呼吸暂停（无缺氧；分离5 分钟）同时监测膈吸气输出。用脊髓 RARa 抑制剂预处理会削弱复发性中枢性呼吸暂停触发膈吸气输出长期持续增加的能力，但在用 RAR/抑制剂预处理的大鼠中表现出可塑性。在没有减少呼吸神经活动的情况下，鞘内 RA 应用引起膈吸气输出增加，这可以通过用 RARa 抑制剂预处理来防止。这些数据表明脊髓 RARa 激活对于由呼吸神经活动反复减少引发的 iMF 是必需的，并且在没有呼吸神经活动剥夺的情况下，膈运动池中/附近的 RARa 激活足以引起膈吸气运动促进。