Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR China; Neurology Department, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, PR China; National Center for Clinical Medicine of Neurological Diseases, Beijing, 100070, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100070, PR China.
National Center for Clinical Medicine of Neurological Diseases, Beijing, 100070, PR China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, 100070, PR China; Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, PR China.
Epilepsy Res. 2022 Nov;187:107027. doi: 10.1016/j.eplepsyres.2022.107027. Epub 2022 Sep 27.
Clinical studies have demonstrated that deep brain stimulation of the anterior nucleus of the thalamus (ANT) is a safe and effective treatment for focal epilepsy and drug-resistant epilepsy. However, the mechanism of action of ANT deep brain stimulation, especially in terms of neuromodulatory circuits, is not fully understood. In this study, we evaluated the anatomical and functional connectivity of the ANT in rats. For anatomical connectivity, herpes simplex virus (HSV) and pseudorabies virus (PRV; Bartha stain) were focally injected into the ANT of rats to label the connected brain structures in the retrograde and anterograde directions, respectively. For functional connectivity, we used c-Fos mapping in conjunction with electrical stimulation of the ANT to map the brain structures functionally connected to the ANT. Circuit connectivity mapping revealed that the ANT was connected to the hippocampus, the nucleus accumbens, the dorsal part of the lateral septal nucleus (LSD), the amygdala, the secondary motor cortex (M2), the cingulate cortex, the substantia nigra, the hypothalamus, and other regions. The ipsilateral connections were stronger than the contralateral connections. Deep brain stimulation of the ANT resulted in c-fos expression in the cortex, hippocampus, amygdala, striatum and hypothalamus, with the strongest activation in the hippocampus. These results suggest that the ANT has a wide range of structural and functional connections, which may underlie the effectiveness of deep brain stimulation in treating epilepsy. DATA AVAILABILITY STATEMENT: The datasets generated for this study are available on request to the corresponding author.
临床研究表明，丘脑前核（ANT）深部脑刺激是治疗局灶性癫痫和耐药性癫痫的一种安全有效的方法。然而，ANT 深部脑刺激的作用机制，特别是在神经调节回路方面，尚未完全理解。在这项研究中，我们评估了大鼠 ANT 的解剖和功能连接。对于解剖连接，单纯疱疹病毒（HSV）和伪狂犬病病毒（PRV；巴氏染色）分别被聚焦注射到大鼠的 ANT 中，以分别标记逆行和顺行方向的连接脑结构。对于功能连接，我们使用 c-Fos 映射结合 ANT 的电刺激来映射与 ANT 功能连接的脑结构。回路连接映射显示，ANT 与海马体、伏隔核、外侧隔核背侧部分（LSD）、杏仁核、次级运动皮层（M2）、扣带回皮层、黑质、下丘脑和其他区域相连。同侧连接比对侧连接更强。ANT 深部脑刺激导致皮层、海马体、杏仁核、纹状体和下丘脑的 c-fos 表达，其中海马体的激活最强。这些结果表明，ANT 具有广泛的结构和功能连接，这可能是深部脑刺激治疗癫痫的有效性的基础。数据可用性声明：本研究生成的数据集可应要求提供给相应的作者。
