Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida, USA.
Department of Psychology, Florida Atlantic University, Boca Raton, Florida, USA.
Hippocampus. 2021 Jul;31(7):756-769. doi: 10.1002/hipo.23302. Epub 2021 Jan 21.
The nucleus reuniens (RE) and rhomboid (RH) nuclei of the ventral midline thalamus are reciprocally connected with the prefrontal cortex (PFC) and the hippocampus (HF) and serve as key intermediaries between these structures, regulating cognitive and emotional behaviors. Regarding affective behavior, several recent reports have described the involvement of RE/RH in the acquisition and retention of conditioned fear, but little is known regarding their role (RE/RH) in anxiety-like behaviors. We examined the role of RH/RE on avoidance and defensive behaviors in male Long Evans rats using the elevated plus maze (EPM). We found that the reversible suppression of RE/RH with muscimol increased avoidance behavior to the open arms of the plus maze as shown by: (a) significant reductions in open arm entries; (b) reductions in the mean duration of time spent in the open arms; and (c) significant increases in retreats during open arm exploration. This was coupled with decreases in the number of head dips in the maze. Consistent with these behavioral effects, a single exposure of naïve rats to the plus maze produced significant increases in c-fos expression selectively in RE and RH of midline thalamic nuclei. We posit that RE/RH normally acts to optimize adaptive responses to anxiety-eliciting situations, and disruptions of RE/RH produce severe deficits in coping behaviors-or as shown here increases in avoidance/defensive behaviors. In sum, the present results establish a novel role for RE/RH in anxiety-like avoidance behavior. In addition to its role in attention, working memory, and executive control, RE/RH also regulates adaptative responses to not only fear but also to anxiogenic stimuli. As such, dysfunction of RE/RH may contribute to the amalgamation of symptoms common to many mental health disorders including anxiety, depression, schizophrenia, and PTSD.
中缝背核（RE）和菱形核（RH）是腹侧中线丘脑的核团，与前额叶皮层（PFC）和海马（HF）相互连接，是这些结构之间的关键中介，调节认知和情绪行为。关于情感行为，最近有几项报道描述了 RE/RH 在条件性恐惧的获得和保留中的参与，但对于它们在类焦虑行为中的作用知之甚少。我们使用高架十字迷宫（EPM）检查了 RH/RE 在雄性 Long Evans 大鼠回避和防御行为中的作用。我们发现，使用 muscimol 可逆性抑制 RE/RH 会增加大鼠对高架十字迷宫开臂的回避行为，表现为：（a）开臂进入次数显著减少；（b）在开臂上花费的时间平均持续时间减少；（c）在开臂探索期间，撤退次数显著增加。这伴随着迷宫中头下降次数的减少。与这些行为效应一致，单次暴露于高架十字迷宫会导致中缝背核中线丘脑核内 c-fos 表达显著增加。我们假设，RE/RH 通常作用于优化对引起焦虑的情况的适应性反应，而 RE/RH 的破坏会导致应对行为严重缺陷-或者如这里所示，回避/防御行为增加。总之，本研究结果确立了 RE/RH 在类焦虑回避行为中的新作用。除了在注意力、工作记忆和执行控制中的作用外，RE/RH 还调节了对恐惧以及焦虑刺激的适应性反应。因此，RE/RH 的功能障碍可能导致许多精神健康障碍（包括焦虑、抑郁、精神分裂症和 PTSD）的常见症状的融合。
