Departments of Neuroscience, Psychiatry and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
Neuropsychopharmacology. 2022 Jul;47(8):1513-1522. doi: 10.1038/s41386-022-01333-1. Epub 2022 Apr 29.
The nucleus reuniens of the thalamus (RE) is a pivotal area responsible for the connectivity of the prefrontal-hippocampus pathway that regulates cognitive, executive, and fear learning processes. Recently, it was proposed that the RE participates in the pathophysiological states related to affective dysregulation. We investigated the role of RE in motivational behavioral and electrophysiological dysregulation induced by stress. Adult Sprague-Dawley rats were exposed to a combination of stressors (restraint stress+footshock) for 10 days and tested one to two weeks later in the forced swim test (FST), ventral tegmental area (VTA)dopamine (DA) neuron electrophysiological activity, and hippocampal-nucleus accumbens plasticity. The RE was inactivated by injecting TTX prior to the procedures. The stress exposure increased the immobility in the FST and decreased VTA DA neuron population activity. Whereas an early long-term potentiation (e-LTP) in the ventral hippocampus-nucleus accumbens pathway was found after fimbria high-frequency stimulation in naïve animals, stressed animals showed an early long-term depression (e-LTD). Inactivation of the RE reversed the stress-induced changes in the FST and restored dopaminergic activity. RE inactivation partially recovered the stress-induced abnormal hippocampal-accumbens plasticity observed in controls. Our findings support the role of the RE in regulating affective dysregulation and blunted VTA DA system function induced by stress. Also, it points to the hippocampal-accumbens pathway as a potential neural circuit through which RE could modulate activity. Therefore, RE may represent a key brain region involved in the neurobiology of amotivational states and may provide insights into circuit dysfunction and markers of the maladaptive stress response.
丘脑核团（RE）是负责调节认知、执行和恐惧学习过程的前额叶-海马途径连接的关键区域。最近，有人提出 RE 参与与情感失调相关的病理生理状态。我们研究了 RE 在应激诱导的动机行为和电生理失调中的作用。成年 Sprague-Dawley 大鼠接受 10 天的应激源（束缚应激+足底电击）组合处理，然后在强迫游泳测试（FST）、腹侧被盖区（VTA）多巴胺（DA）神经元电生理活动和海马-伏隔核可塑性中进行测试一到两周。在进行这些程序之前，通过注射 TTX 使 RE 失活。应激暴露增加了 FST 中的不动性，降低了 VTA DA 神经元群体活动。虽然在未处理的动物中，海马脚高频刺激后发现了腹侧海马-伏隔核通路中的早期长时程增强（e-LTP），但应激动物表现出早期长时程抑制（e-LTD）。RE 失活逆转了 FST 中应激引起的变化，并恢复了多巴胺能活动。RE 失活部分恢复了对照组中观察到的应激诱导的海马-伏隔核异常可塑性。我们的研究结果支持 RE 在调节情感失调和应激引起的 VTA DA 系统功能迟钝中的作用。此外，它指出了海马-伏隔核通路作为一个潜在的神经回路，通过该回路，RE 可以调节活动。因此，RE 可能代表一个与动机状态神经生物学相关的关键脑区，并可能为电路功能障碍和适应不良应激反应的标志物提供见解。
