Zhou Hong, Xiang Wei, Huang Mengbing
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Behav Neurosci. 2021 Oct 21;15:743484. doi: 10.3389/fnbeh.2021.743484. eCollection 2021.
Zona incerta (ZI), a largely inhibitory subthalamic region connected with many brain areas, has been suggested to serve as an integrative node for modulation of behaviors and physiological states, such as fear memory conditioning and aversion responses. It is, however, unclear whether ZI regulated the repeated social defeat stress (RSDS)-induced social conditioned place aversion (CPA) and post-traumatic stress disorder (PTSD)-like behaviors. In this study, the function of ZI was silenced via bilateral injection of tetanus toxin light chain (Tet-tox), a neurotoxin that completely blocks the evoked synaptic transmissions, expressing adeno-associated viruses (AAVs). We found ZI silencing: (1) significantly blocked the expression of RSDS-induced social CPA with no effect on the innate preference; (2) significantly enhanced the anxiety level in mice experienced RSDS with no effect on the locomotion activity; (3) altered the PTSD-associated behaviors, including the promotion of spatial cognitive impairment and the preventions of PPI deficit and social avoidance behavior. These effects were not observed on non-stressed mice. In summary, our results suggest the important role of ZI in modulating RSDS-induced social CPA and PTSD-like behaviors.
未定带（ZI）是丘脑底的一个主要起抑制作用的区域，与许多脑区相连，有人认为它是调节行为和生理状态（如恐惧记忆条件反射和厌恶反应）的整合节点。然而，尚不清楚ZI是否调节重复社会挫败应激（RSDS）诱导的社会条件性位置厌恶（CPA）和创伤后应激障碍（PTSD）样行为。在本研究中，通过双侧注射破伤风毒素轻链（Tet-tox）使ZI功能沉默，Tet-tox是一种完全阻断诱发突触传递的神经毒素，它表达腺相关病毒（AAV）。我们发现沉默ZI：（1）显著阻断RSDS诱导的社会CPA的表达，对先天偏好无影响；（2）显著提高经历RSDS的小鼠的焦虑水平，对运动活动无影响；（3）改变与PTSD相关的行为，包括促进空间认知障碍以及预防感觉门控缺陷和社会回避行为。在未应激的小鼠中未观察到这些效应。总之，我们的结果表明ZI在调节RSDS诱导的社会CPA和PTSD样行为中起重要作用。
