Heterosynaptic Long-Term Potentiation at GABAergic Synapses of Spinal Lamina I Neurons
Heterosynaptic Long-Term Potentiation at GABAergic Synapses of Spinal Lamina I Neurons
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DOI：
10.1523/jneurosci.3076-11.2011
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发表时间：
2011-11-30
影响因子：
5.3
通讯作者：
Sandkuehler, Juergen
中科院分区：
文献类型：
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作者：
Fenselau, Henning;Heinke, Bernhard;Sandkuehler, Juergen
脊髓背角椎板 I 中的神经元在伤害感受中发挥着关键作用，其很大程度上取决于兴奋性和抑制性输入之间的适当平衡。突触强度的任何改变都可能挑战这种微妙的平衡。伤害性 C 纤维和 I 层神经元之间谷氨酸能突触的长时程增强 (LTP) 是一种经过深入研究的疼痛放大细胞模型。相比之下，目前对脊髓背角抑制性突触突触强度的长期变化一无所知。使用大鼠脊髓背根切片制备物，我们发现，通过在 C 纤维突触处诱导 LTP 的刺激方案对初级传入纤维进行条件刺激，也会在 GABA 能突触 (LTPGABA) 处触发 LTP。这种 LTPGABA 本质上是异突触的，并且由 I 类代谢型谷氨酸受体的激活介导。 LTPGABA 不需要打开 AMPA/KA 或 NMDA 亚型的离子型谷氨酸受体通道。配对脉冲比、变异系数和微型 IPSC 分析表明 LTPGABA 在突触前表达。一氧化氮作为逆行信使信号介导脊髓抑制性突触 GABA 释放的增加。脊髓伤害感受回路中突触可塑性的这种新形式可能是维持兴奋和抑制之间的相对平衡以及提高伤害感受通路中的信噪比的重要机制。
Neurons in spinal dorsal horn lamina I play a pivotal role for nociception that critically depends on a proper balance between excitatory and inhibitory inputs. Any modification in synaptic strength may challenge this delicate balance. Long-term potentiation (LTP) at glutamatergic synapses between nociceptive C-fibers and lamina I neurons is an intensively studied cellular model of pain amplification. In contrast, nothing is presently known about long-term changes of synaptic strength at inhibitory synapses in the spinal dorsal horn. Using a spinal cord-dorsal root slice preparation from rats, we show that conditioning stimulation of primary afferent fibers with a stimulating protocol that induces LTP at C-fiber synapses also triggered LTP at GABAergic synapses (LTPGABA). This LTPGABA was heterosynaptic in nature and was mediated by activation of group I metabotropic glutamate receptors. Opening of ionotropic glutamate receptor channels of the AMPA/KA or NMDA subtype was not required for LTPGABA. Paired-pulse ratio, coefficient of variation, and miniature IPSCs analysis revealed that LTPGABA was expressed presynaptically. Nitric oxide as a retrograde messenger signal mediated this increase of GABA release at spinal inhibitory synapses. This novel form of synaptic plasticity in spinal nociceptive circuits may be an essential mechanism to maintain the relative balance between excitation and inhibition and to improve the signal-to-noise ratio in nociceptive pathways.