Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy
Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: Role of corticosterone-mediated apical dendritic atrophy
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DOI：
10.1073/pnas.0706679105
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发表时间：
2008-01-08
影响因子：
11.1
通讯作者：
Aghajanian, George K.
中科院分区：
文献类型：
--
作者：
Liu, Rong-Jian;Aghajanian, George K.
形态学研究表明，反复的束缚压力会导致内侧前额叶皮层（mPFC）锥体细胞顶端树突区的选择性萎缩。然而，这种选择性的功能后果仍不清楚。 mPFC 中 V 层锥体神经元的顶端树突是通过血清素 (5-HT) 和下丘脑分泌素 (orexin) 产生增加的兴奋性突触后电流 (EPSC) 的选择性位点。在此基础上，我们假设顶端树突萎缩可能导致 5-HT 和下丘脑分泌素诱导的兴奋反应减弱。在大鼠 mPFC 切片中结合使用全细胞记录和双光子成像，我们能够将同一层 V 锥体神经元的电生理和形态变化关联起来。重复的轻度约束应力会导致 5-HT 和下丘脑分泌素诱导的 EPSC 减少，这种效应与顶端簇树突分支长度和远端簇分支中的棘密度的减少相关。使用应激激素皮质酮进行长期治疗，虽然会降低 5-HT 反应并通常模拟应激的形态效应，但未能显着减少下丘脑分泌素诱导的 EPSC。用糖皮质激素受体拮抗剂 RU486 对应激动物进行预处理可阻止 5-HT 诱导的 EPSC 减少，但不能阻止下丘脑分泌素诱导的 EPSC 的减少，从而加剧了这种差异。我们的结论是：（i）应激诱导的顶端树突萎缩导致对顶端目标兴奋性输入的反应减弱，（ii）与下丘脑分泌素相比，皮质酮在应激诱导的 5-HT 引起的 EPSC 减少中发挥更大的作用，可能反映了两种递质激活的不同途径。
Morphological studies show that repeated restraint stress leads to selective atrophy in the apical dendritic field of pyramidal cells in the medial prefrontal cortex (mPFC). However, the functional consequence of this selectivity remains unclear. The apical dendrite of layer V pyramidal neurons in the mPFC is a selective locus for the generation of increased excitatory postsynaptic currents (EPSCs) by serotonin (5-HT) and hypocretin (orexin). On that basis, we hypothesized that apical dendritic atrophy might result in a blunting of 5-HT- and hypocretin-induced excitatory responses. Using a combination of whole-cell recording and two-photon imaging in rat mPFC slices, we were able to correlate electrophysiological and morphological changes in the same layer V pyramidal neurons. Repeated mild restraint stress produced a decrement in both 5-HT and hypocretin-induced EPSCs, an effect that was correlated with a decrease in apical tuft dendritic branch length and spine density in the distal tuft branches. Chronic treatment with the stress hormone corticosterone, while reducing 5-HT responses and generally mimicking the morphological effects of stress, failed to produce a significant decrease in hypocretin-induced EPSCs. Accentuating this difference, pretreatment of stressed animals with the glucocorticoid receptor antagonist RU486 blocked reductions in 5-HT-induced EPSCs but not hypocretin-induced EPSCs. We conclude: (i) stress-induced apical dendritic atrophy results in diminished responses to apically targeted excitatory inputs and (ii) corticosterone plays a greater role in stress-induced reductions in EPSCs evoked by 5-HT as compared with hypocretin, possibly reflecting the different pathways activated by the two transmitters.