Sernagor E, Chub N, Ritter A, O'Donovan M J
Laboratory of Neural Control, NINDS, NIH, Bethesda, Maryland 20892, USA.
J Neurosci. 1995 Nov;15(11):7452-64. doi: 10.1523/JNEUROSCI.15-11-07452.1995.
The isolated spinal cord of the chick embryo generates episodes of rhythmic bursting in which sartorius (hip flexor) and femorotibialis (knee extensor) motoneurons exhibit characteristic patterns of activity. At the beginning of each cycle both sets of motoneurons discharge synchronously. Following this brief synchronous activation sartorius motoneurons stop firing at the time of peak femorotibialis activity, producing a period of alternation between the two sets of motoneurons. Intracellular recording from motoneurons has suggested that the pause is mediated by a synaptically induced shunt conductance. However, the pharmacological basis for this shunt and the nature of the excitatory drive to motoneurons is unknown. To address these questions we have investigated the pharmacology of the rhythmic, synaptic drive to lumbosacral motoneurons using local and bath application of several excitatory and inhibitory antagonists, and documenting their effects on motor output in E10-E12 chick embryos. Local application of bicuculline or picrotoxin over sartorius motoneurons abolished the pause in firing recorded from the sartorius muscle nerve. As a consequence, the pattern of sartorius and femorotibialis activity was similar and the motoneurons were coactive. The pause in sartorius firing was shortened following local application of the glycine antagonist strychnine the nicotinic, cholinergic antagonists mecamylamine, and dihydro-beta-erythroidine and several excitatory amino acid antagonists. Application of the GABA uptake inhibitor nipecotic acid depressed the slow potentials and discharge recorded from the sartorius muscle nerve. These findings suggest that the pause is determined primarily by synaptic inputs acting at motoneuron GABAA receptors with contributions from glycinergic, cholinergic, and glutamatergic inputs. The actions of locally applied GABA onto spinal neurons are consistent with these findings because the neurotransmitter depolarizes spinal neurons and reduces their input resistance. Local application of bicuculline, but not strychnine, onto segments containing femorotibialis motoneurons altered the amplitude and duration of femorotibialis discharge and changed the profile of the slow potentials recorded from the muscle nerve. This finding implicates GABAergic inputs in the regulation of femorotibialis discharge. The pause in sartorius firing was still present and a pause in firing appeared in each cycle of femorotibialis discharge following bath application of bicuculline or strychnine. The pause in both sets of motoneurons could be abolished by local application of the NMDA receptor antagonist AP-5 onto the motoneurons, but not by local application of bicuculline. This action of AP-5 was in contrast to its activity in normal Tyrode's solution where it shortened the pause slightly.(ABSTRACT TRUNCATED AT 400 WORDS)
鸡胚的离体脊髓会产生节律性爆发活动，其中缝匠肌（髋屈肌）和股胫肌（膝伸肌）运动神经元呈现出特征性的活动模式。在每个周期开始时，两组运动神经元同步放电。在这短暂的同步激活之后，缝匠肌运动神经元在股胫肌活动达到峰值时停止放电，从而在两组运动神经元之间产生一个交替期。对运动神经元进行细胞内记录表明，这种暂停是由突触诱导的分流电导介导的。然而，这种分流的药理学基础以及运动神经元兴奋驱动的性质尚不清楚。为了解决这些问题，我们使用几种兴奋性和抑制性拮抗剂进行局部和浴槽给药，研究了腰荐部运动神经元节律性突触驱动的药理学，并记录了它们对E10 - E12鸡胚运动输出的影响。在缝匠肌运动神经元上局部应用荷包牡丹碱或印防己毒素可消除从缝匠肌神经记录到的放电暂停。结果，缝匠肌和股胫肌的活动模式相似，运动神经元共同活动。局部应用甘氨酸拮抗剂士的宁、烟碱型胆碱能拮抗剂美加明和二氢 - β - 刺桐碱以及几种兴奋性氨基酸拮抗剂后，缝匠肌放电的暂停时间缩短。应用GABA摄取抑制剂尼克酸可抑制从缝匠肌神经记录到的慢电位和放电。这些发现表明，这种暂停主要由作用于运动神经元GABAA受体的突触输入决定，甘氨酸能、胆碱能和谷氨酸能输入也有贡献。局部应用GABA对脊髓神经元的作用与这些发现一致，因为神经递质使脊髓神经元去极化并降低其输入电阻。在含有股胫肌运动神经元的节段上局部应用荷包牡丹碱而非士的宁，会改变股胫肌放电的幅度和持续时间，并改变从肌肉神经记录到的慢电位波形。这一发现表明GABA能输入参与了股胫肌放电的调节。在浴槽中应用荷包牡丹碱或士的宁后，缝匠肌放电的暂停仍然存在，并且在股胫肌放电的每个周期中都会出现放电暂停。局部应用NMDA受体拮抗剂AP - 5到运动神经元上可消除两组运动神经元的暂停，但局部应用荷包牡丹碱则不能。AP - 5的这种作用与其在正常台氏液中的活性相反，在正常台氏液中它会略微缩短暂停时间。（摘要截断于400字）
