Low frequency stimulation of entorhinal cortex inhibits hippocampal neuronal activities and fast kindling seizures
作者单位：Zhejiang University Department of Pharmacology Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology College of Pharmaceutical Sciences School of Medicine
会议名称：《中国神经科学学会第十届全国学术会议》
会议日期：2013年
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
基 金：supported by the NSF of China(81030061,81221003,81273492) Chinese Postdoctoral Science Foundation(2013M531476) Zhejiang Province Postdoctoral Science Foundation Excellent Postdoctor(BSH1301034)
关 键 词：epilepsy low-frequency stimulation entorhinal cortex kindling
摘 要：Objective The entorhinal cortex（EC） is a potential target for low frequency stimulation（LFS,1Hz）treatment of temporal lobe epilepsy（TLE）.However,the neuronal basis of LFS at EC is unclear.Basing on the anatomy of entorhinal-hippocampal circuit,the present study was designed to determine whether LFS at EC interfere with hippocampal neural activities and seizures.Method The effects of LFS at EC on the neural activity of dentate gyrus（DG） were examined using single-unit extracellular recordings in anesthetized rats and mice.The effect of LFS at EC on hippocampal fast kindling seizures was tested.Results The spontaneous activity of the majority neurons（104/115 neurons） in DG were repeatedly interrupted as soon as LFS-on and quickly backed to baseline after LFS-off.EC stimulation pulse mainly induced two distinct types of neural response in DG:the commonly observed type（81/115neurons） displayed a 179±12 ms inhibition of neural firing 13±2 ms after stimulation;the second type（23/115 neurons）firstly displayed an excitatory response and then a 130±15 ms inhibition of neural firing 25±5 ms after stimulation.This effect of EC stimulation on DG neural activities were mimicked by stimulation of the main projections from the EC to DG（perforant pathway,PP） or optogenetic selective stimulation of axonal projections in DG.LFS of EC also interrupted neurons in hippocampal CA3 and CA1 but not in substantia nigra.Furthermore,LFS of EC immediately after kindling stimulation but not after the cessation of afterdischarge interfered with kindling and kindled seizures.Conclusion LFS of EC directly interrupted the spontaneous activity hippocampal neural activities,which may through its axonal projections to the hippocampus;and LFS of EC interferes with hippocampal fast kindling seizures in a time-dependent aspect.These results suggest EC is a promising target for closed-loop LFS treatment of TLE.