Basting Tyler M, Burke Peter G R, Kanbar Roy, Viar Kenneth E, Stornetta Daniel S, Stornetta Ruth L, Guyenet Patrice G
Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, and.
Department of Pharmaceutical Sciences, Lebanese American University, Beyrouth, Lebanon.
J Neurosci. 2015 Jan 14;35(2):527-43. doi: 10.1523/JNEUROSCI.2923-14.2015.
In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.
在清醒的哺乳动物中，低氧或高碳酸血症会刺激呼吸，而理论上对中枢呼吸化学感受器（CRCs）产生相反的影响。我们通过研究低氧和高碳酸血症如何改变延髓头端腹外侧网状核（RTN）的活动来验证这一理论，RTN被认为是一种呼吸化学感受器和化学反射整合器。在麻醉大鼠中，通过光可逆性沉默表达古紫质（Arch）的RTN神经元。我们用Arch（PRSx8-ArchT-EYFP-LVV）双侧转导RTN和附近的C1神经元，并测量在常氧、低氧或高氧状态下清醒大鼠中Arch激活（10秒）对心肺功能的影响。在非快速眼动睡眠和安静觉醒期间，RTN光抑制对呼吸的抑制作用相同。与常氧相比，在高氧（65% FiO₂）时呼吸频率降低幅度（Δf(R)）更大，在15% FiO₂时较小，在12% FiO₂时无变化。潮气量变化（ΔV(T)）遵循相同趋势。低氧对Δf(R)的影响不依赖于觉醒，但通过使血液重新酸化（乙酰唑胺；3% FiCO₂）可使其逆转。在动脉血pH（pHa）达到7.5之前，Δf(R)与动脉血pH高度相关，在pHa 7.53以上则无频率抑制。血压仅有轻微降低，提示C1神经元受到的抑制非常轻微。总之，RTN神经元在睡眠和觉醒期间对平静呼吸的调节作用相当。RTN神经元是清醒哺乳动物中首个被低碳酸血症性低氧明显沉默的假定呼吸化学感受器。RTN神经元在pHa 7.5以上时沉默，在该值以下时活性增加。在高氧期间，尽管颈动脉体不活动，但RTN激活仍能维持呼吸。最后，在低碳酸血症性低氧期间，颈动脉体刺激通过绕过RTN的途径增加呼吸频率。
