Kinkead R, Zhan W Z, Prakash Y S, Bach K B, Sieck G C, Mitchell G S
Unité de Recherche en Pédiatrie, Centre Hôspitalier Universitaire de Québec, Pavillon St-François d'Assise, Québec, QC G1L 3L5 Canada.
J Neurosci. 1998 Oct 15;18(20):8436-43. doi: 10.1523/JNEUROSCI.18-20-08436.1998.
We tested the hypothesis that spinal plasticity elicited by chronic bilateral cervical dorsal rhizotomy (C3-C5; CDR) has functional implications for respiratory motor control. Surgery was performed on rats (CDR or sham-operated) 26 d before phrenic motoneurons were retrogradely labeled with cholera toxin. Rats were killed 2 d later, and their spinal cords were harvested and processed to reveal the cholera toxin-labeled phrenic motoneurons and serotonin-immunoreactive terminals. The number of serotonin-immunoreactive terminals within 5 micrometer of labeled phrenic motoneuron soma and primary dendrites increased 2.1-fold after CDR versus sham-operation. Time-dependent phrenic motor responses to hypoxia were compared among CDR, sham-operated, and control rats. Anesthetized, paralyzed, vagotomized, and artificially ventilated rats were exposed to three, 5 min episodes of isocapnic hypoxia (FiO2 = 0.11), separated by 5 min hyperoxic intervals (FiO2 = 0.5). One hour after hypoxia, a long-lasting, serotonin-dependent enhancement of phrenic motor output (long-term facilitation) was observed in both sham and control rats. After CDR, long-term facilitation was 108 and 163% greater than control and sham responses, respectively. Pretreatment of CDR rats with a 5-HT2 receptor antagonist (ketanserin tartrate, 2 mg/kg, i.v.) before episodic hypoxia prevented long-term facilitation and revealed a modest (-28 +/- 13%; p < 0.05) long-lasting depression of phrenic motor output. The results indicate that CDR: (1) increases serotonergic innervation of the phrenic motor nucleus; and (2) augments serotonin-dependent long-term facilitation of phrenic motor output. These results further suggest a form of plasticity based on changes in the capacity for neuromodulation.
慢性双侧颈背根切断术（C3 - C5；CDR）引发的脊髓可塑性对呼吸运动控制具有功能影响。在膈运动神经元用霍乱毒素进行逆行标记前26天，对大鼠实施手术（CDR组或假手术组）。2天后处死大鼠，取出其脊髓并进行处理，以显示霍乱毒素标记的膈运动神经元和5-羟色胺免疫反应性终末。与假手术组相比，CDR术后，标记的膈运动神经元胞体和初级树突周围5微米范围内的5-羟色胺免疫反应性终末数量增加了2.1倍。比较了CDR组、假手术组和对照组大鼠对缺氧的膈运动反应随时间的变化。将麻醉、麻痹、迷走神经切断并进行人工通气的大鼠暴露于3次、每次5分钟的等碳酸血症性缺氧（吸入氧分数 = 0.11）中，每次缺氧间隔5分钟的高氧期（吸入氧分数 = 0.5）。缺氧1小时后，在假手术组和对照组大鼠中均观察到膈运动输出的持久、5-羟色胺依赖性增强（长期易化）。CDR术后，长期易化分别比对照组和假手术组反应高108%和163%。在间歇性缺氧前，用5-HT2受体拮抗剂（酒石酸酮色林，2毫克/千克，静脉注射）预处理CDR大鼠，可阻止长期易化，并显示出膈运动输出适度的（-28±13%；p < 0.05）持久抑制。结果表明，CDR：（1）增加了膈运动核的5-羟色胺能神经支配；（2）增强了5-羟色胺依赖性的膈运动输出长期易化。这些结果进一步提示了一种基于神经调节能力变化的可塑性形式。
