Analysis & Control of Non-Synaptic Epileptiform Activity

分析

基本信息

  • 批准号:
    6793142
  • 负责人:
  • 金额:
    $ 22.95万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-09-04 至 2006-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Epilepsy is characterized by the abnormal synchronization of large numbers of neurons. The synchronization and propagation of epileptic seizures are thought to rely on synaptic transmission. However, non-synaptic mechanisms such as neuronal swelling, electric field effects, potassium diffusion, gap junctions and glial cell function also contribute to the generation and spread of epileptiform activity. Non-synaptic epilepsy is generated by lowering calcium in the extracellular space thereby eliminating synaptic transmission. As a result, the clinical relevance of non-synaptic mechanisms has been questioned. We have recently generated novel models of non-synaptic activity in the presence of normal calcium and normal synaptic transmission. We propose to analyze the role of non-synaptic mechanisms in neuronal synchronization in order to understand and potentially develop novel therapies to prevent abnormal neural activity. We have recently shown that the frequency, amplitude and duration of non-synaptic epileptiform events can be controlled independently suggesting that different mechanisms are responsible. In particular, preliminary experiments show that gap junctions are not responsible for the propagation of non-synaptic events generated in zero-calcium medium, but that potassium diffusion (potentially mediated by the activity of glial cells) plays a crucial role. The goal of this proposal is to analyze and control non-synaptic epileptiform activity. Specifically, we propose to 1) determine the common mechanisms underlying three models of non-synaptic epilepsy, 2) establish the conditions sufficient for the generation of non-synaptic epileptogenesis, 3) analyze the mechanisms underlying the propagation of non-synaptic epileptiform activity, 4) develop a computer model of non-synaptic propagation to test hypotheses not directly testable by experimentation, and 5) develop methods for controlling epileptiform activity. Multi-disciplinary experimental approaches such as computer simulation and fluorescence imaging will be combined with pharmacology and in-vitro slice electrophysiology to achieve these goals. Current therapeutic agents are not capable of controlling seizure activity in 25 percent of all epileptic patients. The results of our studies should provide valuable insight into mechanisms underlying epileptogenesis as well as new tools for the control and suppression of epileptic seizures.
描述(由申请人提供):癫痫的特征是异常的 大量神经元的同步。同步和 癫痫发作的传播被认为依赖于突触传递。 然而,非突触机制,如神经元肿胀,电场 影响,钾扩散,缝隙连接和神经胶质细胞功能也 有助于癫痫样活动的产生和传播。非突触 癫痫是通过降低细胞外间隙中的钙而产生的, 消除突触传递。因此, 非突触机制受到质疑。我们最近创造了一种新的 在正常钙和正常钙存在下的非突触活动模型 突触传递我们建议分析非突触的作用, 神经元同步的机制,以了解和潜在的 开发新的疗法来防止异常的神经活动。我们最近 显示非突触性癫痫样放电的频率、幅度和持续时间 事件可以独立控制,这表明不同的机制 责任特别是,初步实验表明,间隙连接是 不负责非突触事件的传播, 零钙培养基,但钾扩散(可能由 神经胶质细胞的活性)起着至关重要的作用。本提案的目的是 分析和控制非突触癫痫样活动。 具体来说,我们建议1)确定三个基础的共同机制 非突触性癫痫模型,2)建立足够的条件, 非突触性癫痫发生的产生; 3)分析其发生机制 潜在的非突触癫痫样活动的传播,4)发展一个 非突触传播的计算机模型来测试假设, 通过实验测试,5)开发控制方法 癫痫样活动多学科实验方法,如 计算机模拟和荧光成像将与药理学相结合 和体外切片电生理学来实现这些目标。电流 治疗剂不能控制25例癫痫发作 占所有癫痫患者的百分比。我们的研究结果应该提供 对癫痫发生机制的有价值的见解以及新的 控制和抑制癫痫发作的工具。

项目成果

期刊论文数量(14)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mechanism of highly synchronized bilateral hippocampal activity.
  • DOI:
    10.1016/j.expneurol.2013.11.014
  • 发表时间:
    2014-01
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Wang, Y.;Toprani, S.;Tang, Y.;Vrabec, T.;Durand, D. M.
  • 通讯作者:
    Durand, D. M.
Can the shape of attractor forbid chaotic phase synchronization?
吸引子的形状能否禁止混沌相位同步?
Diffusive coupling can induce synchronized periodic activity in neural networks.
扩散耦合可以引起神经网络中的同步周期性活动。
A high aspect ratio microelectrode array for mapping neural activity in vitro.
  • DOI:
    10.1016/j.jneumeth.2011.11.027
  • 发表时间:
    2012-03-15
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Kibler, Andrew B.;Jamieson, Brian G.;Durand, Dominique M.
  • 通讯作者:
    Durand, Dominique M.
Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation.
  • DOI:
    10.1016/j.expneurol.2015.04.001
  • 发表时间:
    2015-07
  • 期刊:
  • 影响因子:
    5.3
  • 作者:
    Ladas TP;Chiang CC;Gonzalez-Reyes LE;Nowak T;Durand DM
  • 通讯作者:
    Durand DM
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DOMINIQUE M DURAND其他文献

DOMINIQUE M DURAND的其他文献

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{{ truncateString('DOMINIQUE M DURAND', 18)}}的其他基金

Seizure control by electric field control
通过电场控制进行咬合控制
  • 批准号:
    10641916
  • 财政年份:
    2021
  • 资助金额:
    $ 22.95万
  • 项目类别:
Seizure control by electric field control
通过电场控制进行咬合控制
  • 批准号:
    10365510
  • 财政年份:
    2021
  • 资助金额:
    $ 22.95万
  • 项目类别:
Cellular and Neural Network Mechanism of Transcranial Electric Stimulation
经颅电刺激的细胞和神经网络机制
  • 批准号:
    10338804
  • 财政年份:
    2021
  • 资助金额:
    $ 22.95万
  • 项目类别:
Non-Invasive Oropharynx Appliance to Maintain Airway Patency
用于保持气道通畅的非侵入性口咽器具
  • 批准号:
    9906411
  • 财政年份:
    2020
  • 资助金额:
    $ 22.95万
  • 项目类别:
Low-frequency stimulation of fiber tracts to control seizures
低频刺激纤维束以控制癫痫发作
  • 批准号:
    10059285
  • 财政年份:
    2019
  • 资助金额:
    $ 22.95万
  • 项目类别:
Low-frequency stimulation of fiber tracts to control seizures
低频刺激纤维束以控制癫痫发作
  • 批准号:
    10517517
  • 财政年份:
    2019
  • 资助金额:
    $ 22.95万
  • 项目类别:
Low-frequency stimulation of fiber tracts to control seizures
低频刺激纤维束以控制癫痫发作
  • 批准号:
    10300055
  • 财政年份:
    2019
  • 资助金额:
    $ 22.95万
  • 项目类别:
Detection and Control of Epilepsy
癫痫的检测和控制
  • 批准号:
    8139519
  • 财政年份:
    2008
  • 资助金额:
    $ 22.95万
  • 项目类别:
Detection and Control of Epilepsy
癫痫的检测和控制
  • 批准号:
    8711567
  • 财政年份:
    2008
  • 资助金额:
    $ 22.95万
  • 项目类别:
Detection and Control of Epilepsy
癫痫的检测和控制
  • 批准号:
    9096236
  • 财政年份:
    2008
  • 资助金额:
    $ 22.95万
  • 项目类别:

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