Department of Psychological and Brain Sciences, Institute for Neuroscience, Texas A&M University, College Station, Texas 77843, USA.
Learn Mem. 2022 Jul 28;29(8):216-222. doi: 10.1101/lm.053611.122. Print 2022 Aug.
Recent data reveal that the thalamic nucleus reuniens (RE) has a critical role in the extinction of conditioned fear. Muscimol (MUS) infusions into the RE impair within-session extinction of conditioned freezing and result in poor long-term extinction memories in rats. Although this suggests that RE inactivation impairs extinction learning, it is also possible that it is involved in the consolidation of extinction memories. To examine this possibility, we examined the effects of RE inactivation on the consolidation and reconsolidation of fear extinction in male and female rats. Twenty-four hours after auditory fear conditioning, rats underwent an extinction procedure (45 CS-alone trials) in a novel context and were infused with saline (SAL) or MUS within minutes of the final extinction trial. Twenty-four hours later, conditioned freezing to the extinguished CS was assessed in the extinction context. Postextinction inactivation of the RE did not affect extinction retrieval. In a second experiment, rats underwent extinction training and, 24 h later, were presented with a single CS to reactivate the extinction memory; rats were infused with SAL or MUS immediately after the reactivation session. Pharmacological inactivation of the RE did not affect conditioned freezing measured in a drug-free retrieval test the following day. Importantly, we found in a subsequent test that MUS infusions immediately before retrieval testing increased conditioned freezing and impaired extinction retrieval, as we have previously reported. These results indicate that although RE inactivation impairs the expression of extinction, it does not impair either the consolidation or reconsolidation of extinction memories. We conclude that the RE may have a critical role in suppressing context-inappropriate fear memories in the extinction context.
最近的数据显示,丘脑中间核(RE)在条件性恐惧的消除中起着关键作用。将 muscimol(MUS)注入 RE 会损害条件性冻结的单次疗程内消退,并导致大鼠的长期消退记忆不佳。尽管这表明 RE 失活会损害消退学习,但也有可能它参与了消退记忆的巩固。为了检验这种可能性,我们研究了 RE 失活对雄性和雌性大鼠恐惧消退的巩固和再巩固的影响。在听觉恐惧条件作用后 24 小时,大鼠在新环境中进行消退程序(45 个 CS-单独试验),并在最后一次消退试验后的几分钟内接受盐水(SAL)或 MUS 输注。24 小时后,在消退环境中评估对消退 CS 的条件性冻结。RE 的术后失活并不影响消退检索。在第二个实验中,大鼠进行了消退训练,24 小时后,用单个 CS 重新激活消退记忆;大鼠在重新激活会话后立即接受 SAL 或 MUS 输注。RE 的药理学失活不影响在随后的无药物检索测试中测量的条件性冻结。重要的是,我们在随后的测试中发现,在检索测试前立即输注 MUS 会增加条件性冻结并损害消退检索,正如我们之前报道的那样。这些结果表明,尽管 RE 失活会损害消退的表达,但不会损害消退记忆的巩固或再巩固。我们得出的结论是,RE 可能在抑制消退环境中不适当的上下文恐惧记忆方面起着关键作用。