Mitra Rupshi, Jadhav Shantanu, McEwen Bruce S, Vyas Ajai, Chattarji Sumantra
National Centre for Biological Sciences, Bangalore 560065, India.
Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9371-6. doi: 10.1073/pnas.0504011102. Epub 2005 Jun 20.
It has long been hypothesized that morphological and numerical alterations in dendritic spines underlie long-term structural encoding of experiences. Here we investigate the efficacy of aversive experience in the form of acute immobilization stress (AIS) and chronic immobilization stress (CIS) in modulating spine density in the basolateral amygdala (BLA) of male rats. We find that CIS elicits a robust increase in spine density across primary and secondary branches of BLA spiny neurons. We observed this CIS-induced spinogenesis in the BLA 1 d after the termination of CIS. In contrast, AIS fails to affect spine density or dendritic arborization when measured 1 d later. Strikingly, the same AIS causes a gradual increase in spine density 10 d later but without any effect on dendritic arbors. Thus, by modulating the duration of immobilization stress, it is possible to induce the formation of new spines without remodeling dendrites. However, unlike CIS-induced spine formation, the gradual increase in spine density 10 d after a single exposure to AIS is localized on primary dendrites. Finally, this delayed induction of BLA spinogenesis is paralleled by a gradual development of anxiety-like behavior on the elevated plus-maze 10 d after AIS. These findings demonstrate that stressful experiences can lead to the formation of new dendritic spines in the BLA, which is believed to be a locus of storage for fear memories. Our results also suggest that stress may facilitate symptoms of chronic anxiety disorders like post-traumatic stress disorder by enhancing synaptic connectivity in the BLA.
长期以来,人们一直假设树突棘的形态和数量变化是经验长期结构编码的基础。在这里,我们研究了以急性固定应激(AIS)和慢性固定应激(CIS)形式存在的厌恶经验对雄性大鼠基底外侧杏仁核(BLA)中棘密度的调节作用。我们发现,CIS会导致BLA棘状神经元的初级和次级分支上的棘密度显著增加。我们在CIS终止后1天在BLA中观察到这种由CIS诱导的树突棘形成。相比之下,1天后测量时,AIS未能影响棘密度或树突分支。令人惊讶的是,相同的AIS在10天后会导致棘密度逐渐增加,但对树突分支没有任何影响。因此,通过调节固定应激的持续时间,可以在不重塑树突的情况下诱导新棘的形成。然而,与CIS诱导的棘形成不同,单次暴露于AIS后10天棘密度的逐渐增加局限于初级树突上。最后,AIS后10天在高架十字迷宫上焦虑样行为的逐渐发展与BLA树突棘形成的延迟诱导平行。这些发现表明,应激经历可导致BLA中形成新的树突棘,而BLA被认为是恐惧记忆的存储位点。我们的结果还表明,应激可能通过增强BLA中的突触连接来促进创伤后应激障碍等慢性焦虑症的症状。