Septal Signaling Suppresses Seizures Through Stimulating Somatostatin Cells.
Septal Signaling Suppresses Seizures Through Stimulating Somatostatin Cells.
复制标题
DOI：
10.1177/1535759720949240
复制
发表时间：
2020-09
影响因子：
3.6
通讯作者：
Forcelli PA
中科院分区：
文献类型：
--
作者：
Forcelli PA
Direct Septum-Hippocampus Cholinergic Circuit Attenuates Seizure Through Driving Somatostatin Inhibition Wang Y，Wang Y，Xu C，Wang S，Tan N，Chen C，Chen L，Wu X，Fei F，Cheng H，Lin W，Qi Y，Chen B，Liang J，Zhao J，Xu Z，Guo Y，Zhang S，Li X，Zhou Y，Duan S，Chen Z.生物精神病学2020;87（9）：843-856。doi：10.1016/j.biopsych.2019.11.014。以往的研究表明胆碱能神经元参与癫痫发作，然而，内侧隔（MS）-海马胆碱能回路在颞叶癫痫（TLE）的具体作用尚未完全阐明。本研究应用磁共振成像和弥散张量成像技术对42例TLE患者和22例健康志愿者的MS-海马回路进行了研究。利用光遗传学和化学遗传学，结合体内或体外电生理学和逆行狂犬病病毒追踪，我们揭示了一个直接的MS-海马胆碱能回路，通过驱动生长抑素抑制动物TLE模型中的癫痫发作。我们发现与健康人相比，伴有海马硬化的TLE患者MS-海马的神经纤维连接减少。在小鼠TLE模型中，MS胆碱能神经元在海马癫痫发作期间停止放电。MS胆碱能神经元的光遗传和化学发生激活（但不是谷氨酸能或GABA能[γ-氨基丁酸能]神经元）显著减弱海马癫痫发作，而特异性抑制促进海马癫痫发作。电生理学结合狂犬病毒示踪研究表明，直接（而不是间接）MS-海马胆碱能投射介导的抗癫痫作用，优先针对海马GABA能神经元。此外，海马生长抑素阳性（而不是小清蛋白阳性）的GABA能神经元亚型的化学发生抑制逆转了MS-海马胆碱能回路的抗癫痫效应，这是通过激活生长抑素阳性神经元来模仿的。这些发现强调了TLE中直接胆碱能MS-海马回路通过驱动下游生长激素抑制素效应器而具有显着的抗癫痫作用。这可能会更好地了解癫痫发作回路的变化和癫痫的精确时空控制。
Direct Septum-Hippocampus Cholinergic Circuit Attenuates Seizure Through Driving Somatostatin Inhibition Wang Y, Wang Y, Xu C, Wang S, Tan N, Chen C, Chen L, Wu X, Fei F, Cheng H, Lin W, Qi Y, Chen B, Liang J, Zhao J, Xu Z, Guo Y, Zhang S, Li X, Zhou Y, Duan S, Chen Z. Biol Psychiatry. 2020;87(9):843-856. doi:10.1016/j.biopsych.2019.11.014. Previous studies indicated the involvement of cholinergic neurons in seizure; however, the specific role of the medial septum (MS)–hippocampus cholinergic circuit in temporal lobe epilepsy (TLE) has not yet been completely elucidated. In the current study, we used magnetic resonance imaging and diffusion tensor imaging to characterize the pathological change of the MS-hippocampus circuit in 42 patients with TLE compared with 22 healthy volunteers. Using optogenetics and chemogenetics, combined with in vivo or in vitro electrophysiology and retrograde rabies virus tracing, we revealed a direct MS-hippocampus cholinergic circuit that potently attenuates seizure through driving somatostatin inhibition in animal TLE models. We found that patients with TLE with hippocampal sclerosis showed a decrease of neuronal fiber connectivity of the MS-hippocampus compared with healthy people. In the mouse TLE model, MS cholinergic neurons ceased firing during hippocampal seizures. Optogenetic and chemogenetic activation of MS cholinergic neurons (but not glutamatergic or GABAergic [γ-aminobutyric acidergic] neurons) significantly attenuated hippocampal seizures, while specific inhibition promoted hippocampal seizures. Electrophysiology combined with modified rabies virus tracing studies showed that direct (but not indirect) MS-hippocampal cholinergic projections mediated the anti-seizure effect by preferentially targeting hippocampal GABAergic neurons. Furthermore, chemogenetic inhibition of hippocampal somatostatin-positive (rather than parvalbumin-positive) subtype of GABAergic neurons reversed the anti-seizure effect of the MS-hippocampus cholinergic circuit, which was mimicked by activating somatostatin-positive neurons. These findings underscore the notable anti-seizure role of the direct cholinergic MS-hippocampus circuit in TLE through driving the downstream somatostatin effector. This may provide a better understanding of the changes of the seizure circuit and the precise spatiotemporal control of epilepsy.”
登录
查看更多内容
影响因子：
3.7
作者：
Nagode DA;Tang AH;Karson MA;Klugmann M;Alger BE
通讯作者：
Alger BE
与 Theta 状态相关的间隔胆碱能神经元的放电通过毒蕈碱受体扰乱海马波纹振荡
影响因子：
5.3
作者：
Ma，Xiaoyu;Zhang，Yiyao;Xu，Jiamin
通讯作者：
Xu，Jiamin
影响因子：
3.3
作者：
Ferencz, I;Leanza, G;Lindvall, O
通讯作者：
Lindvall, O
影响因子：
16.6
作者：
通讯作者：
--
影响因子：
4.7
作者：
Hillert, Markus H.;Imran, Imran;Klein, Jochen
通讯作者：
Klein, Jochen