Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability
Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability
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颗粒细胞的内在重新缩放恢复了癫痫过度兴奋期间齿状回网络模型的模式分离能力
DOI：
10.1002/hipo.22373
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
Wolfart J
中科院分区：
文献类型：
--
作者：
Yim MY;Hanuschkin A;Wolfart J
齿状回（DG）被认为可以通过模式分离实现有效的海马记忆获取。通过将模式定义为时空分布的动作电位序列，主要的 DG 输出神经元（颗粒细胞，GC）可能会稀疏并将相似的输入模式与穿孔路径 (PP) 分开。在电生理学实验中，我们已经证明，在颞叶癫痫 (TLE) 期间，GC 通过“泄漏”通道的转录上调来降低其兴奋性。在这里，我们研究了这种细胞类型特异性的内在可塑性是否能够稳态地调整 DG 网络功能。我们修改了已建立的基于电导的 DG 网络计算机模型，使其实现时空模式分离任务，并在有和没有实验约束的泄漏 GC 表型的情况下量化其性能。两种拟议的 TLE 癫痫机制以不同程度和组合实施：通过苔藓纤维萌芽进行反复 GC 激发和增加 PP 输入。虽然增加 PP 强度只会逐渐降低图案分离度，但发芽的轻微升高已经显着（非线性）损害了图案分离度。在大多数经过测试的超兴奋网络中，GC 泄漏改善了模式分离。然而，在一些具有全或无癫痫行为的发芽情况下，无论有或没有泄漏GC，模式分离都被禁用。在非线性损伤的轻度萌芽（和 PP 增加）区域，泄漏 GC 在恢复模式分离性能方面特别有效。这些结果与实验观察到的 GC 内在重新缩放有助于维持 DG 网络的生理功能的假设相一致。 © 2014 Wiley 期刊公司。
The dentate gyrus (DG) is thought to enable efficient hippocampal memory acquisition via pattern separation. With patterns defined as spatiotemporally distributed action potential sequences, the principal DG output neurons (granule cells, GCs), presumably sparsen and separate similar input patterns from the perforant path (PP). In electrophysiological experiments, we have demonstrated that during temporal lobe epilepsy (TLE), GCs downscale their excitability by transcriptional upregulation of “leak” channels. Here we studied whether this cell type‐specific intrinsic plasticity is in a position to homeostatically adjust DG network function. We modified an established conductance‐based computer model of the DG network such that it realizes a spatiotemporal pattern separation task, and quantified its performance with and without the experimentally constrained leaky GC phenotype. Two proposed TLE seizure mechanisms were implemented in various degrees and combinations: recurrent GC excitation via mossy fiber sprouting and increased PP input. While increasing PP strength degraded pattern separation only gradually, already the slight elevation of sprouting drastically (non‐linearly) impaired pattern separation. In most tested hyperexcitable networks, leaky GCs ameliorated pattern separation. However, in some sprouting situations with all‐or‐none seizure behavior, pattern separation was disabled with and without leaky GCs. In the mild sprouting (and PP increase) region of non‐linear impairment, leaky GCs were particularly effective in restoring pattern separation performance. These results are compatible with the hypothesis that the experimentally observed intrinsic rescaling of GCs serves to maintain the physiological function of the DG network. © 2014 Wiley Periodicals, Inc.
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影响因子：
3
作者：
Santoro A
通讯作者：
Santoro A
通过突触和内在抑制机制实现神经元兴奋性的稳态
DOI：
10.1093/med/9780199322299.003.0004
发表时间：
2015
期刊：
影响因子：
--
作者：
Meier JC;Semtner M;Wolfart J
通讯作者：
Wolfart J
影响因子：
5.3
作者：
Kirchheim F;Tinnes S;Haas CA;Stegen M;Wolfart J
通讯作者：
Wolfart J
影响因子：
3.7
作者：
Stegen, Michael;Kirchheim, Florian;Wolfart, Jakob
通讯作者：
Wolfart, Jakob
DOI：
10.1002/9780470975039.ch14
发表时间：
2011
期刊：
--
影响因子：
--
作者：
W. Tatum
通讯作者：
W. Tatum