Regulation of gephyrin cluster size and inhibitory synaptic currents on Renshaw cells by motor axon excitatory inputs
Regulation of gephyrin cluster size and inhibitory synaptic currents on Renshaw cells by motor axon excitatory inputs
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DOI：
10.1523/jneurosci.3725-04.2005
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发表时间：
2005-01-12
影响因子：
5.3
通讯作者：
Alvarez, FJ
中科院分区：
文献类型：
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作者：
Gonzalez-Forero, D;Pastor, AM;Alvarez, FJ
Renshaw 细胞接收高密度的抑制性突触，其特征是大的突触后 gephyrin 簇和具有大峰值振幅和长衰减的混合甘氨酸能/GABA 能抑制电流。这些特性似乎适合提高对伦肖细胞的抑制功效，并通过未知的机制在出生后成熟。我们测试了这样的假设：兴奋性运动轴突输入的异质突触影响调节伦肖细胞抑制性突触的发育。因此，在出生后第5天（P5）肌内注射破伤风（TeNT）和肉毒杆菌神经毒素A（BoNT-A），以分别提高或降低运动轴突放电活动约2周。注射 TeNT 后，Renshaw 细胞上的平均 gephyrin 簇面积在 P15 时增加了 18.4%，在 P20 时增加了 28.4%，而在注射 BoNT-A 后，在 P15 时减少了 17.7%，在 P20 时减少了 19.9%。平均大小差异是由小和大gephyrin簇的比例变化造成的。 P5 TeNT 注射后 P9-P15 Renshaw 细胞的全细胞记录显示，与对照组相比，甘氨酸微型突触后电流 (mPSC) 的峰值幅度和混合（甘氨酸/GABA 能）mPSC 的快速成分增加（分别为 60.9% 和 78.9%）。 GABA 能 mPSC 的峰值振幅增加幅度较小 (45.8%)。然而，由于突触 GABA 能电流的衰减相对较长，TeNT 后突触甘氨酸和 GABA(A) 受体的总电流转移变化相似（分别增加 56% 和 48.9%）。我们得出结论，运动轴突兴奋性突触活动调节 Renshaw 细胞抑制性突触特性的发展，影响突触后 gephyrin 和甘氨酸受体的募集，并在较小程度上影响 GABA(A) 受体。
Renshaw cells receive a high density of inhibitory synapses characterized by large postsynaptic gephyrin clusters and mixed glycinergic/GABAergic inhibitory currents with large peak amplitudes and long decays. These properties appear adapted to increase inhibitory efficacy over Renshaw cells and mature postnatally by mechanisms that are unknown. We tested the hypothesis that heterosynaptic influences from excitatory motor axon inputs modulate the development of inhibitory synapses on Renshaw cells. Thus, tetanus (TeNT) and botulinum neurotoxin A (BoNT-A) were injected intramuscularly at postnatal day 5 (P5) to, respectively, elevate or reduce motor axon firing activity for similar to2 weeks. After TeNT injections, the average gephyrin cluster areas on Renshaw cells increased by 18.4% at P15 and 28.4% at P20 and decreased after BoNT-A injections by 17.7% at P15 and 19.9% at P20. The average size differences resulted from changes in the proportions of small and large gephyrin clusters. Whole-cell recordings in P9-P15 Renshaw cells after P5 TeNT injections showed increases in the peak amplitude of glycinergic miniature postsynaptic currents (mPSCs) and the fast component of mixed (glycinergic/GABAergic) mPSCs compared with controls (60.9% and 78.9%, respectively). GABAergic mPSCs increased in peak amplitude to a smaller extent (45.8%). However, because of the comparatively longer decays of synaptic GABAergic currents, total current transfer changes after TeNT were similar for synaptic glycine and GABA(A) receptors (56 vs 48.9% increases, respectively). We concluded that motor axon excitatory synaptic activity modulates the development of inhibitory synapse properties on Renshaw cells, influencing recruitment of postsynaptic gephyrin and glycine receptors and, to lesser extent, GABA(A) receptors.