Department of Pharmacology, National Cheng Kung University, Tainan 70101, Taiwan.
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
J Neurosci. 2021 Feb 10;41(6):1317-1330. doi: 10.1523/JNEUROSCI.1751-20.2020. Epub 2020 Dec 11.
In social animals, the behavioral and hormonal responses to stress can be transmitted from one individual to another through a social transmission process, and, conversely, social support ameliorates stress responses, a phenomenon referred to as social buffering. Metaplasticity represents activity-dependent synaptic changes that modulate the ability to elicit subsequent synaptic plasticity. Authentic stress can induce hippocampal metaplasticity, but whether transmitted stress has the same ability remains unknown. Here, using an acute restraint-tailshock stress paradigm, we report that both authentic and transmitted stress in adult male mice trigger metaplastic facilitation of long-term depression (LTD) induction at hippocampal CA1 synapses. Using LTD as a readout of persistent synaptic consequences of stress, our findings demonstrate that, in a male-male dyad, stress transmission happens in nearly half of naive partners and stress buffering occurs in approximately half of male stressed mice that closely interact with naive partners. By using a social-confrontation tube test to assess the dominant-subordinate relationship in a male-male dyad, we found that stressed subordinate mice are not buffered by naive dominant partners and that stress transmission is exhibited in ∼60% of dominant naive partners. Furthermore, the appearance of stress transmission correlates with more time spent in sniffing the anogenital area of stressed mice, and the appearance of stress buffering correlates with more time engaged in allogrooming from naive partners. Chemical ablation of the olfactory epithelium with dichlobenil or physical separation between social contacts diminishes stress transmission. Together, our data demonstrate that transmitted stress can elicit metaplastic facilitation of LTD induction as authentic stress. Social animals can acquire information about their environment through interactions with conspecifics. Stress can induce enduring changes in neural activity and synaptic function. Current studies are already unraveling the transmission and buffering of stress responses between individuals, but little is known about the relevant synaptic changes associated with social transmission and buffering of stress. Here, we show that authentic and transmitted stress can prime glutamatergic synapses onto hippocampal CA1 neurons to undergo long-term depression. This hippocampal metaplasticity is bufferable following social interactions with naive partners. Hierarchical status of naive partners strongly affects the social buffering effect on synaptic consequences of stress. This work provides novel insights into the conceptual framework for synaptic changes with social transmission and buffering of stress.
在社交动物中，个体通过社会传递过程，将应激的行为和激素反应从一个个体传递到另一个个体，反之，社会支持可以减轻应激反应，这种现象称为社会缓冲。代谢可塑性代表了依赖于活动的突触变化，这些变化调节了引发后续突触可塑性的能力。真正的压力会引起海马体的代谢可塑性，但传递的压力是否具有相同的能力尚不清楚。在这里，我们使用急性束缚-尾巴刺激应激范式，报告了成年雄性小鼠中的真正应激和传递应激都会触发海马 CA1 突触中长时程压抑（LTD）诱导的代谢可塑性增强。我们使用 LTD 作为应激对突触持续后果的读出，发现，在雄性-雄性对偶中，应激传递发生在大约一半的未受应激的伙伴中，应激缓冲发生在大约一半与未受应激的伙伴密切互动的受应激的雄性中。通过使用社交对抗管测试来评估雄性-雄性对偶中的支配-从属关系，我们发现，受应激的从属雄性不会被未受应激的支配雄性缓冲，并且在大约 60%的未受应激的支配雄性中会出现应激传递。此外，应激传递的出现与花费更多时间嗅探受应激雄性的肛殖区有关，而应激缓冲的出现与未受应激的伙伴进行更多的异体梳理有关。用二氯苯氧氯乙烷化学消融嗅上皮或社交接触的物理分离会减少应激传递。总之，我们的数据表明，传递的应激可以引发与真正应激相同的 LTD 诱导的代谢可塑性增强。社交动物可以通过与同种个体的互动来获取有关其环境的信息。应激可以诱导神经活动和突触功能的持久变化。目前的研究已经在揭示个体之间应激反应的传递和缓冲，但对于与应激的社会传递和缓冲相关的相关突触变化知之甚少。在这里，我们表明，真正的和传递的应激可以使谷氨酸能突触对海马 CA1 神经元进行长时程压抑。这种海马代谢可塑性在与未受应激的伙伴进行社交互动后是可缓冲的。未受应激的伙伴的层次结构地位强烈影响社交缓冲对应激的突触后果的影响。这项工作为社交传递和缓冲应激的突触变化提供了新的见解。
