Medial temporal lobe epilepsy (MTLE) is among the most common and most drug-resistant types of epilepsies associated with remodeling of the trisynaptic circuit of the hippocampus. The cornu ammonis (CA)3 region, as the "pacemaker" of the circuit, and CA3 → CA1 synapse (Schaffer collaterals) are potential targets for suppression of MTLE. We examined optogenetic manipulation of CA3 neurons in controlling the perforant pathway kindled seizures. One week after implantation of stimulating electrodes in perforant pathway, a recording electrode in CA1, and an optic fiber in CA3, rats underwent rapid kindling procedure. A lentivector with capability to move in retrograde monosynaptic direction and to insert the gene of red light sensitive opsin Jaws in neurons was injected into CA1 of the kindled rats. One week later, the kindled rats were stimulated at afterdischarge (AD) threshold under red light illumination to CA3; and duration of AD (ADD), generalized seizures (S5D), and total seizure behavior (SD) were recorded. Encoding Jaws in CA1, CA3, and entorhinal neuronal cells of the vector injected rats was verified by immunohistochemistry. More than 90% of CA1, CA3, and entorhinal neurons of the counted sections expressed Jaws. Red light (625 nm) illumination to CA3 of the kindled rats expressing Jaws entirely suppressed generalized seizures and significantly diminished ADD and SD. Encoding the light-sensitive chloride pump Jaws in the CA3, is an efficient optogenetic strategy to stop perforant pathway kindled seizures.

中文翻译：

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将大白鲨插入CA3神经元细胞后，通过光抑制CA3激发光通路控制癫痫发作。

颞叶内侧癫痫（MTLE）是与海马三突触回路重塑相关的最常见和最耐药的癫痫类型之一。角u（CA）3区域，作为回路的“起搏器”，以及CA3→CA1突触（Schaffer侧支）是抑制MTLE的潜在目标。我们检查了CA3神经元的光遗传学操纵，以控制穿孔途径引起的癫痫发作。大鼠在穿孔途径中植入刺激电极，CA1中的记录电极和CA3中的光纤植入后一周，大鼠进行了快速点燃过程。将能在逆向单突触方向移动并在神经元中插入红光敏感视蛋白下颌基因的慢病毒载体注入点燃的大鼠的CA1中。一周后，点燃的大鼠在红光照射下以放电后阈值刺激至CA3。记录AD持续时间（ADD），全身性癫痫发作（S5D）和总癫痫发作行为（SD）。通过免疫组织化学验证了载体注射的大鼠的CA1，CA3和内嗅神经元细胞中的编码爪。计数切片中超过90％的CA1，CA3和内嗅神经元表达了下颌。对表达下颌的被点燃大鼠的CA3发出的红光（625 nm）完全抑制了全身性癫痫发作，并显着降低了ADD和SD。在CA3中对光敏氯化物泵钳进行编码，是一种有效的光遗传学策略，可以阻止穿孔途径引起的癫痫发作。记录总癫痫发作行为（SD）。通过免疫组织化学验证了载体注射的大鼠的CA1，CA3和内嗅神经元细胞中的编码爪。计数切片中超过90％的CA1，CA3和内嗅神经元表达了下颌。对表达下颌的被点燃大鼠的CA3发出的红光（625 nm）完全抑制了全身性癫痫发作，并显着降低了ADD和SD。在CA3中对光敏氯化物泵钳进行编码，是一种有效的光遗传学策略，可以阻止穿孔途径引起的癫痫发作。记录总癫痫发作行为（SD）。通过免疫组织化学验证了载体注射的大鼠的CA1，CA3和内嗅神经元细胞中的编码爪。计数切片中超过90％的CA1，CA3和内嗅神经元表达了下颌。对表达下颌的被点燃大鼠的CA3发出的红光（625 nm）完全抑制了全身性癫痫发作，并显着降低了ADD和SD。在CA3中对光敏氯化物泵钳进行编码，是一种有效的光遗传学策略，可以阻止穿孔途径引起的癫痫发作。对表达下颌的被点燃大鼠的CA3发出的红光（625 nm）完全抑制了全身性癫痫发作，并显着降低了ADD和SD。在CA3中对光敏氯化物泵钳进行编码，是一种有效的光遗传学策略，可以阻止穿孔途径引起的癫痫发作。对表达下颌的被点燃大鼠的CA3发出的红光（625 nm）完全抑制了全身性癫痫发作，并显着降低了ADD和SD。在CA3中对光敏氯化物泵钳进行编码，是一种有效的光遗传学策略，可以阻止穿孔途径引起的癫痫发作。