Selective Activation of Microglia Facilitates Synaptic Strength
Selective Activation of Microglia Facilitates Synaptic Strength
复制标题
DOI：
10.1523/jneurosci.2061-14.2015
复制
发表时间：
2015-03-18
影响因子：
5.3
通讯作者：
Sandkuehler, Juergen
中科院分区：
文献类型：
--
作者：
Clark, Anna K.;Gruber-Schoffnegger, Doris;Sandkuehler, Juergen
突触可塑性被认为仅由神经元启动，其中流行的观点认为神经胶质细胞仅指定突触传递和可塑性的支持功能。我们现在证明，神经胶质细胞可以控制突触强度独立的神经元活动。在这里，我们表明，在大鼠中的小胶质细胞的选择性激活是足以迅速促进初级传入C-纤维和I层神经元之间的突触强度，在伤害性通路中的第一个突触中继。具体而言，通过fractalkine激活CX3CR1受体诱导小胶质细胞释放白细胞介素-1 β，其调节突触后神经元中的NMDA信号传导，导致类花生酸信使的释放，其最终增强突触前神经递质释放。与传统观点相反，这种形式的可塑性不需要增强的神经元活动来触发导致突触易化的事件。伤害性通路中突触强度的增强代表了疼痛放大的细胞模型。因此，目前的数据表明，在慢性疼痛状态下，CX3CR1介导的小胶质细胞激活驱动促进背角中的兴奋性突触传递，这有助于慢性疼痛状态下的疼痛超敏反应。
Synaptic plasticity is thought to be initiated by neurons only, with the prevailing view assigning glial cells mere specify supportive functions for synaptic transmission and plasticity. We now demonstrate that glial cells can control synaptic strength independent of neuronal activity. Here we show that selective activation of microglia in the rat is sufficient to rapidly facilitate synaptic strength between primary afferent C-fibers and lamina I neurons, the first synaptic relay in the nociceptive pathway. Specifically, the activation of the CX3CR1 receptor by fractalkine induces the release of interleukin-1 beta from microglia, which modulates NMDA signaling in postsynaptic neurons, leading to the release of an eicosanoid messenger, which ultimately enhances presynaptic neurotransmitter release. In contrast to the conventional view, this form of plasticity does not require enhanced neuronal activity to trigger the events leading to synaptic facilitation. Augmentation of synaptic strength in nociceptive pathways represents a cellular model of pain amplification. The present data thus suggest that, under chronic pain states, CX3CR1-mediated activation of microglia drives the facilitation of excitatory synaptic transmission in the dorsal horn, which contributes to pain hypersensitivity in chronic pain states.