Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77845, USA; Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX 77845, USA.
Department of Psychological Science, University of Texas Rio Grande Valley, TX 78539.
Behav Brain Res. 2024 Jul 26;470:115071. doi: 10.1016/j.bbr.2024.115071. Epub 2024 May 26.
The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials. First, we examined whether VH inactivation would affect ITRs. Male rats underwent SAA training and subsequently received intra-VH infusions of saline or muscimol before retrieval tests in the training context. Rats that received muscimol performed significantly fewer ITRs, but equivalent avoidance responses, compared to controls. Next, we asked whether chemogenetic VH activation would increase ITR vigor. In male and female rats expressing excitatory (hM3Dq) DREADDs, systemic CNO administration produced a robust ITR increase that was not due to nonspecific locomotor effects. Then, we examined whether chemogenetic VH activation potentiated ITRs in an alternate (non-training) test context and found it did. Finally, to determine if context-US associations mediate ITRs, we exposed rats to the training context for three days after SAA training to extinguish the context. Rats submitted to context extinction did not show a reliable decrease in ITRs during a retrieval test, suggesting that context-US associations are not responsible for ITRs. Collectively, these results reveal an important role for the VH in context-dependent ITRs during SAA. Further work is required to explore the neural circuits and associative basis for these responses, which may be underlie pathological avoidance that occurs in humans after threat has passed.
海马体在调节记忆中的上下文过程中起着核心作用。我们已经表明，腹侧海马体（VH）的药理学失活减弱了大鼠信号主动回避（SAA）的上下文依赖性。在这里，我们探讨了 VH 是否介导了试验间反应（ITRs），这是在试验之间发生的假定未强化的回避反应。首先，我们检查了 VH 失活是否会影响 ITRs。雄性大鼠接受 SAA 训练，然后在训练环境中的检索测试前接受 VH 内盐水或 muscimol 输注。与对照组相比，接受 muscimol 的大鼠表现出明显较少的 ITR，但回避反应相同。接下来，我们询问化学遗传 VH 激活是否会增加 ITR 的活力。在表达兴奋性（hM3Dq）DREADD 的雄性和雌性大鼠中，全身 CNO 给药会产生强烈的 ITR 增加，这不是由于非特异性运动效应引起的。然后，我们检查了化学遗传 VH 激活是否会增强替代（非训练）测试环境中的 ITR，结果发现会增强。最后，为了确定上下文-US 关联是否介导 ITRs，我们在 SAA 训练后三天将大鼠暴露于训练环境中以消除上下文。在检索测试中，接受上下文灭绝的大鼠没有表现出 ITRs 的可靠减少，这表明上下文-US 关联不是 ITRs 的原因。总之，这些结果揭示了 VH 在 SAA 期间依赖于上下文的 ITRs 中的重要作用。需要进一步的工作来探索这些反应的神经回路和联想基础，这可能是人类在威胁过去后发生病理性回避的基础。
