Impaired Neuronal Operation through Aberrant Intrinsic Plasticity in Epilepsy
Impaired Neuronal Operation through Aberrant Intrinsic Plasticity in Epilepsy
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DOI：
10.1002/ana.24348
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发表时间：
2015-04-01
影响因子：
11.2
通讯作者：
Crepel, Valerie
中科院分区：
文献类型：
--
作者：
Artinian, Julien;Peret, Angelique;Crepel, Valerie
颞叶癫痫患者常表现为认知共病，并伴有反复发作。然而，颞叶癫痫神经元信息处理受损的细胞机制仍然知之甚少。在海马结构内，神经元网络经历重大重组，包括齿状回中苔藓纤维的发芽;它们在齿状颗粒细胞之间建立异常的复发性突触，并通过突触后红藻氨酸受体进行操作。在这份报告中，我们测试的假设，这种异常的本地电路改变的信息处理构成的主要兴奋性传入通路从内嗅皮层到齿状颗粒celles.MethodsExperiments的穿孔路径输入进行了控制大鼠和大鼠颞叶癫痫盐酸匹鲁卡品治疗诱导的齿状颗粒细胞。神经元记录在膜片钳在整个细胞配置在海马slice.ResultsOur目前的数据显示，红藻氨酸受体的突触输入的异常读出触发了癫痫齿状回颗粒细胞的穿孔路径输入输出操作的长期损害。我们证明，这是由于异常的活动依赖性增强的持续钠电流改变固有的放电特性的齿状回颗粒celles.InterpretationWe建议，这种异常的活动依赖性的内在可塑性，持久地损害了信息处理的皮质输入在齿状回，可能参与到大脑皮层相关的认知缺陷，如癫痫患者的报告。《神经病学年鉴》2015;77：592-606
ObjectivePatients with temporal lobe epilepsy often display cognitive comorbidity with recurrent seizures. However, the cellular mechanisms underlying the impairment of neuronal information processing remain poorly understood in temporal lobe epilepsy. Within the hippocampal formation neuronal networks undergo major reorganization, including the sprouting of mossy fibers in the dentate gyrus; they establish aberrant recurrent synapses between dentate granule cells and operate via postsynaptic kainate receptors. In this report, we tested the hypothesis that this aberrant local circuit alters information processing of perforant path inputs constituting the major excitatory afferent pathway from entorhinal cortex to dentate granule cells.MethodsExperiments were performed in dentate granule cells from control rats and rats with temporal lobe epilepsy induced by pilocarpine hydrochloride treatment. Neurons were recorded in patch clamp in whole cell configuration in hippocampal slices.ResultsOur present data revealed that an aberrant readout of synaptic inputs by kainate receptors triggered a long-lasting impairment of the perforant path input-output operation in epileptic dentate granule cells. We demonstrated that this is due to the aberrant activity-dependent potentiation of the persistent sodium current altering intrinsic firing properties of dentate granule cells.InterpretationWe propose that this aberrant activity-dependent intrinsic plasticity, which lastingly impairs the information processing of cortical inputs in dentate gyrus, may participate in hippocampal-related cognitive deficits, such as those reported in patients with epilepsy. Ann Neurol 2015;77:592-606