Kinkead Richard, Balon Norbert, Genest Sophie-Emmanuelle, Gulemetova Roumiana, Laforest Sylvie, Drolet Guy
Pediatrics Research Unit, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada.
Eur J Neurosci. 2008 Mar;27(5):1174-88. doi: 10.1111/j.1460-9568.2008.06082.x.
Neonatal maternal separation (NMS) alters respiratory control development. Adult male rats previously subjected to NMS show a hypoxic ventilatory response 25% greater than controls. During hypoxia, gamma-aminobutyric acid (GABA) release within the nucleus tractus solitarius (NTS) modulates the magnitude of the ventilatory response. Because development of GABAergic receptors is sensitive to NMS, we tested the hypothesis that in adults, a change in responsiveness to GABA within the NTS contributes to NMS-related enhancement of the inspiratory (phrenic) response to hypoxia. Pups subjected to NMS were placed in an incubator for 3 h/day for 10 consecutive days [postnatal days 3 to 12]. Controls were undisturbed. Adult (8-10 weeks old) rats were anaesthetized (urethane; 1.6 g/kg), paralysed and artificially ventilated to record phrenic activity. Rats either received a 50-nL microinjection of GABA (5 microm) or phosphate-buffered saline (sham) within the caudal NTS, or no injection prior to being exposed to hypoxia (FiO(2) = 0.12; 5 min). NMS enhanced both the frequency and amplitude components of the phrenic response to hypoxia vs controls. GABA microinjection attenuated the phrenic responses in NMS rats only. This result is supported by ligand binding autoradiography results showing that the number of GABA(A) receptors within the NTS was 69% greater in NMS vs controls. Despite this increase, the phrenic response to hypoxia of NMS rats is larger than controls, suggesting that the higher responsiveness to GABA microinjection within the NTS is part of a mechanism that aims to compensate for: (i) a deficient GABAergic modulation; (ii) enhancement of excitatory inputs converging onto this structure; or (iii) both.
新生鼠母婴分离（NMS）会改变呼吸控制的发育。先前经历过NMS的成年雄性大鼠表现出比对照组高25%的低氧通气反应。在低氧期间，孤束核（NTS）内γ-氨基丁酸（GABA）的释放调节通气反应的幅度。由于GABA能受体的发育对NMS敏感，我们检验了这样一个假设：在成年大鼠中，NTS内对GABA反应性的变化促成了与NMS相关的对低氧吸气（膈神经）反应的增强。经历过NMS的幼崽在出生后第3至12天连续10天每天置于培养箱中3小时。对照组未受干扰。成年（8至10周龄）大鼠用乌拉坦（1.6 g/kg）麻醉、麻痹并进行人工通气以记录膈神经活动。大鼠在暴露于低氧（FiO₂ = 0.12；5分钟）之前，要么在尾侧NTS内接受50 nL GABA（5微摩尔）或磷酸盐缓冲盐水（假注射）的微量注射，要么不进行注射。与对照组相比，NMS增强了对低氧的膈神经反应的频率和幅度成分。GABA微量注射仅减弱了NMS大鼠的膈神经反应。配体结合放射自显影结果支持了这一结果，该结果显示NMS大鼠NTS内GABA(A)受体的数量比对照组多69%。尽管有这种增加，NMS大鼠对低氧的膈神经反应仍大于对照组，这表明NTS内对GABA微量注射更高的反应性是一种旨在补偿以下情况的机制的一部分：（i）GABA能调节不足；（ii）汇聚到该结构上的兴奋性输入增强；或（iii）两者兼有。
