Yasmin Farhana, Saxena Kapil, McEwen Bruce S, Chattarji Sumantra
National Centre for Biological Sciences, Bangalore, India.
Centre for Brain Development and Repair, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India.
Physiol Rep. 2016 Oct;4(20). doi: 10.14814/phy2.13002.
There is growing evidence that stress leads to contrasting patterns of structural plasticity in the hippocampus and amygdala, two brain areas implicated in the cognitive and affective symptoms of stress-related psychiatric disorders. Acute stress has been shown to trigger a delayed increase in the density of dendritic spines in the basolateral amygdala (BLA) of rodents. However, the physiological correlates of this delayed spinogenesis in the BLA remain unexplored. Furthermore, NMDA receptors (NMDARs) have been known to underlie chronic stress-induced structural plasticity in the hippocampus, but nothing is known about the role of these receptors in the delayed spinogenesis, and its physiological consequences, in the BLA following acute stress. Here, using whole-cell recordings in rat brain slices, we find that a single exposure to 2-h immobilization stress enhances the frequency, but not amplitude, of miniature excitatory postsynaptic currents (mEPSCs) recorded from principal neurons in the BLA 10 days later. This was also accompanied by faster use-dependent block of NMDA receptor currents during repeated stimulation of thalamic inputs to the BLA, which is indicative of higher presynaptic release probability at these inputs 10 days later. Furthermore, targeted in vivo infusion of the NMDAR-antagonist APV into the BLA during the acute stress prevents the increase in mEPSC frequency and spine density 10 days later. Together, these results identify a role for NMDARs during acute stress in both the physiological and morphological strengthening of synaptic connectivity in the BLA in a delayed fashion. These findings also raise the possibility that activation of NMDA receptors during stress may serve as a common molecular mechanism despite the divergent patterns of plasticity that eventually emerge after stress in the amygdala and hippocampus.
越来越多的证据表明，压力会导致海马体和杏仁核出现相反的结构可塑性模式，这两个脑区与压力相关精神疾病的认知和情感症状有关。急性应激已被证明会引发啮齿动物基底外侧杏仁核（BLA）中树突棘密度的延迟增加。然而，BLA中这种延迟的树突棘生成的生理相关性仍未得到探索。此外，已知NMDA受体（NMDARs）是海马体中慢性应激诱导的结构可塑性的基础，但对于这些受体在急性应激后BLA中延迟的树突棘生成及其生理后果中的作用却一无所知。在这里，我们使用大鼠脑片的全细胞记录发现，单次暴露于2小时的束缚应激会在10天后增强从BLA中的主要神经元记录到的微小兴奋性突触后电流（mEPSCs）的频率，但不影响其幅度。这还伴随着在反复刺激丘脑输入到BLA期间，NMDA受体电流更快的使用依赖性阻断，这表明10天后这些输入处的突触前释放概率更高。此外，在急性应激期间将NMDAR拮抗剂APV靶向注入BLA可防止10天后mEPSC频率和树突棘密度的增加。总之，这些结果确定了NMDARs在急性应激期间对BLA中突触连接的生理和形态强化的延迟作用。这些发现还提出了一种可能性，即尽管杏仁核和海马体在应激后最终出现的可塑性模式不同，但应激期间NMDA受体的激活可能是一种共同的分子机制。
