Neuroscience Program, Brain Institute, Tulane University, New Orleans, Louisiana, 70118.
Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, 70118.
Hippocampus. 2017 Sep;27(9):1016-1029. doi: 10.1002/hipo.22749. Epub 2017 Jul 3.
Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.
创伤后应激障碍（PTSD）的特征是创伤后出现记忆障碍。急性捕食者威胁已成为 PTSD 的一种行为模型，但捕食者气味对与长期记忆相关的信号级联的影响仍知之甚少。在这项研究中，我们让雄性和雌性 Wistar 大鼠暴露于合成捕食者气味 2,5-二氢-2,4,5-三甲基噻唑啉（TMT）中，以评估行为和生理反应，以及快速调节与学习和记忆相关的信号转导级联在雄性和雌性海马体中。在 TMT 在家中的暴露过程中，雄性和雌性动物都表现出强烈的不动性、回避和随时间变化的活动改变。从生理学上讲，TMT 暴露增加了雄性和雌性啮齿动物的循环皮质酮和血糖，表明 TMT 引起了与性别无关的行为和生理反应。就信号转导而言，TMT 暴露迅速降低了雄性海马体中环磷腺苷反应元件结合蛋白（CREB）的磷酸化，但雌性海马体中没有。此外，TMT 暴露降低了雄性海马体中细胞外信号调节激酶 1/2 的磷酸化并增加了突触核信使蛋白 Jacob 的核表达，与 CREB 关闭途径的激活一致。在后续的行为实验中，训练后暴露于 TMT 并不影响雄性大鼠的空间水迷宫表现。然而，重新引入到先前呈现 TMT 的环境中的雄性大鼠表现出回避和过度活跃，但没有冻结行为或皮质酮反应升高，表明 TMT 暴露支持一种不表现为不动性的情境条件作用。总之，我们的研究结果表明，TMT 会引起雄性和雌性 Wistar 大鼠相似的行为和生理反应，但会影响雄性和雌性海马体中不同的信号级联，这可能导致与捕食者暴露相关的行为中断。
