Reduced Glutamatergic Currents and Dendritic Branching of Layer 5 Pyramidal Cells Contribute to Medial Prefrontal Cortex Deactivation in a Rat Model of Neuropathic Pain.
Reduced Glutamatergic Currents and Dendritic Branching of Layer 5 Pyramidal Cells Contribute to Medial Prefrontal Cortex Deactivation in a Rat Model of Neuropathic Pain.
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DOI：
10.3389/fncel.2016.00133
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发表时间：
2016
影响因子：
5.3
通讯作者：
Martina M
中科院分区：
文献类型：
--
作者：
Kelly CJ;Huang M;Meltzer H;Martina M
多项研究表明，神经病理性疼痛与多个脑区的重大重组有关。与慢性疼痛强烈的情绪突显相一致，边缘系统的参与显得尤为重要。在过去的几年里，人们已经清楚地看到，前额叶皮质(PFC)的功能失活对疼痛的认知/情绪和感觉成分都是至关重要的。然而，在细胞水平上，这种失活的细节在很大程度上仍然不清楚。在这里，我们显示了周围神经病理性损伤(备用神经损伤模型)后1周，大鼠内侧前额叶皮质第5层(L5)的锥体细胞对兴奋性谷氨酸能输入的反应减少了约50%，自发兴奋性突触电流的频率也降低。此外，这些电池降低了膜电容，增加了输入电阻。所有这些发现与树突长度的减少是一致的，因此我们对记录的神经元的一个子集进行了详细的形态分析。我们发现SNI动物胞体近端的顶端树突(不包括簇状突起)较短且不太复杂，这与电容和谷氨酸能输入的减少一致。最后，我们采用体内微透析法比较了假手术组和SNI组大鼠前额叶皮质谷氨酸和GABA的基础浓度，发现SNI组大鼠的环境谷氨酸水平降低。综上所述，这些数据表明，谷氨酸能传递受损导致神经病理性疼痛中mPFC的功能失活。此外，L5锥体神经元顶端树突的分支减少可能是慢性疼痛中灰质减少的基础。
Multiple studies have demonstrated that neuropathic pain is associated with major reorganization in multiple brain areas. In line with the strong emotional salience of chronic pain, involvement of the limbic system appears particularly important. Within the past few years, it has become clear that the functional deactivation of the prefrontal cortex (PFC) is critical for both the cognitive/emotional and the sensory components of pain. However, at the cellular level, details of this deactivation remain in large part unclear. Here we show that 1 week after a peripheral neuropathic injury (Spared Nerve Injury model) pyramidal cells in layer 5 (L5) of the rat medial PFC show responses to excitatory glutamatergic inputs that are reduced by about 50%, as well as reduced frequency of spontaneous excitatory synaptic currents. Additionally, these cells have reduced membrane capacitance and increased input resistance. All these findings are consistent with decreased dendritic length, thus we performed a detailed morphological analysis on a subset of the recorded neurons. We found that the apical dendrites proximal to the soma (excluding the tuft) are shorter and less complex in SNI animals, in agreement with the reduced capacitance and glutamatergic input. Finally, we used in vivo microdialysis to compare the basal concentrations of glutamate and GABA in the PFC of sham and SNI rats and found that ambient glutamate is decreased in SNI rats. Taken together, these data show that impaired glutamatergic transmission contributes to the functional deactivation of the mPFC in neuropathic pain. Additionally, the reduced branching of apical dendrites of L5 pyramidal neurons may underlay the gray matter reduction in chronic pain.