Optogenetic stimulus-triggered acquisition of seizure resistance
Optogenetic stimulus-triggered acquisition of seizure resistance
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DOI：
10.1016/j.nbd.2021.105602
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发表时间：
2022-02-01
影响因子：
6.1
通讯作者：
Matsui，Ko
中科院分区：
文献类型：
--
作者：
Shimoda，Yoshiteru;Beppu，Kaoru;Matsui，Ko
与电路不同，大脑的硬件很容易改变。重复的脑电刺激模拟癫痫发生。在这样的“点燃”过程之后，适度的刺激就足以引发严重的癫痫发作。在这里，我们报告光遗传学神经元刺激也可以将大鼠大脑转变为过度兴奋状态。然而，持续的刺激再次将大脑转变为强烈抵抗癫痫发作的状态。组织化学检查表明，中度星形胶质细胞激活与弹性获得一致。给予腺苷 A1 受体拮抗剂后，大脑立即恢复到过度兴奋状态，这表明腺苷抑制了过度兴奋。此外，使用体内微透析证实了基础腺苷的增加。每日神经元到星形胶质细胞的信号传导可能促使腺苷内源性作用的稳态增加。我们的数据表明，某种刺激模式可以使大脑回路对癫痫具有抵抗力，而无需外源性药物给药。
Unlike an electrical circuit, the hardware of the brain is susceptible to change. Repeated electrical brain stimulation mimics epileptogenesis. After such “kindling” process, a moderate stimulus would become sufficient in triggering a severe seizure. Here, we report that optogenetic neuronal stimulation can also convert the rat brain to a hyperexcitable state. However, continued stimulation once again converted the brain to a state that was strongly resistant to seizure induction. Histochemical examinations showed that moderate astrocyte activation was coincident with resilience acquisition. Administration of an adenosine A1 receptor antagonist instantly reverted the brain back to a hyperexcitable state, suggesting that hyperexcitability was suppressed by adenosine. Furthermore, an increase in basal adenosine was confirmed usingin vivomicrodialysis. Daily neuron-to-astrocyte signaling likely prompted a homeostatic increase in the endogenous actions of adenosine. Our data suggest that a certain stimulation paradigm could convert the brain circuit resilient to epilepsy without exogenous drug administration.