【摘 要】
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Although low-frequency stimulation (LFS,<5 Hz) has been an alternative option for the treatment of temporal lobe epilepsy (TLE), the optimal targets and underlying mechanisms remains unclear.Here, usi
【机 构】
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Institute of Neuroscience, Department of Pharmacology,College of Pharmaceutical Sciences, Zhejiang U
【出 处】
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第十六届全国神经精神药理学学术会议
论文部分内容阅读
Although low-frequency stimulation (LFS,<5 Hz) has been an alternative option for the treatment of temporal lobe epilepsy (TLE), the optimal targets and underlying mechanisms remains unclear.Here, using optogenetic-electrophysiological strategy, we demonstrate an antiepileptic neural circuit from the entorhinal cortex (EC) to the hippocampus as a new target for LFS (1 Hz)treatment of hippocampal seizures in TLE.LFS at the EC inhibited hippocampal kindling epileptogenesis, kindled seizures and spontaneous epileptic activities in rodent.Extracellular recording showed every electrical pulse of LFS at the EC transitorily excites about 50% of interneurons and inhibits about 70% of principal cells in the ventral hippocampus.Low-frequency optogenetic photostimulation of the hippo-campal GABAergic system is sufficient to mimic the neural modulatory and antiepileptic effect of LFS at the EC in VGAT-ChR2-EYFP mice.Intrahippocampal injection of GABAergic receptor blockers, especially GABAB receptor blocker CGP35348,abolished those inhibitory effects of LFS.Furthermore,low-frequency optogenetic photo-stimulation of the entorhinal glutamatergic system (in Thy1-ChR2-EYFP mice) but not GABAergic system (in VGAT-ChR2-EYFP mice) exerts similar inhibitory effects as LFS at the EC.These data provide first direct evidence that there exists an antiepileptic neural circuit from the EC to the hippocampus, and it may further serve as an effective target of LFS treatment for TLE.
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