Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.
Activity-dependent structural plasticity after aversive experiences in amygdala and auditory cortex pyramidal neurons.
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DOI：
10.1016/j.neuroscience.2016.04.045
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发表时间：
2016-07-22
期刊：
影响因子：
3.3
通讯作者：
Shansky R
中科院分区：
文献类型：
--
作者：
Gruene T;Flick K;Rendall S;Cho JH;Gray J;Shansky R
大脑是高度可塑的，会对许多经历做出反应。特别是学习可以诱导树突棘的结构重塑，这被认为与记忆的形成有关。经典巴甫洛夫恐惧条件反射（FC）传统上将听觉线索与厌恶性脚冲击配对，并被广泛用于研究联想学习和记忆的神经过程。过去的研究发现，在FC后，树突棘的几个结构发生了变化。但是，由于大脑结构中细胞的异质性和传统神经解剖学技术的局限性，即使已知的电路被隔离，也不清楚是否所有的细胞在学习过程中都是活跃的。在这项研究中，我们采用了一种新颖的方法来明确分析暴露于提示或未提示足震激活的神经元的结构可塑性。我们使用雄性和雌性Arc- dvenus转基因小鼠，它们表达由活动相关的Arc启动子驱动的金星荧光团，以识别在两种情况下都活跃的神经元。然后，我们将荧光显微注射靶向于杏仁核基底外侧区（BLA）和听觉关联皮层（TeA）的Arc+和邻近的Arc−神经元。在BLA和TeA中，与Arc−神经元相比，Arc+神经元的细棘和蘑菇棘密度降低。这种效应在男性和女性中都存在，在有暗示和没有暗示的休克组中也同样存在。总的来说，这项研究增加了我们对神经元活动如何影响结构可塑性的理解，并代表了一种方法上的进步，我们可以直接将结构变化与经验相关的神经活动联系起来。
The brain is highly plastic and undergoes changes in response to many experiences. Learning especially can induce structural remodeling of dendritic spines, which is thought to relate to memory formation. Classical Pavlovian fear conditioning (FC) traditionally pairs an auditory cue with an aversive footshock, and has been widely used to study neural processes underlying associative learning and memory. Past research has found dendritic spine changes after FC in several structures. But, due to heterogeneity of cells within brain structures and limitations of traditional neuroanatomical techniques, it is unclear if all cells included in analyses were actually active during learning processes, even if known circuits are isolated. In this study, we employed a novel approach to analyze structural plasticity explicitly in neurons activated by exposure to either cued or uncued footshocks. We used male and female Arc-dVenus transgenic mice, which express the Venus fluorophore driven by the activity-related Arc promoter, to identify neurons that were active during either scenario. We then targeted fluorescent microinjections to Arc+ and neighboring Arc− neurons in the basolateral area of the amygdala (BLA) and auditory association cortex (TeA). In both BLA and TeA, Arc+ neurons had reduced thin and mushroom spine densities compared to Arc− neurons. This effect was present in males and females alike and also in both cued and uncued shock groups. Overall, this study adds to our understanding of how neuronal activity affects structural plasticity, and represents a methodological advance in the ways we can directly relate structural changes to experience-related neural activity.