文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

颗粒细胞的内在重新缩放可恢复癫痫性高兴奋性期间齿状回网络模型的模式分离能力。

Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability.

作者信息

Yim Man Yi, Hanuschkin Alexander, Wolfart Jakob

机构信息

Department of Mathematics, University of Hong Kong, Hong Kong.

出版信息

Hippocampus. 2015 Mar;25(3):297-308. doi: 10.1002/hipo.22373. Epub 2014 Nov 4.


DOI:10.1002/hipo.22373
PMID:25269417
Abstract

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.

摘要

齿状回(DG)被认为可通过模式分离实现高效的海马体记忆获取。模式被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,GCs)大概会稀疏并分离来自穿通通路(PP)的相似输入模式。在电生理实验中,我们已经证明,在颞叶癫痫(TLE)期间,GCs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调节DG网络功能。我们修改了一个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漏电GC表型的情况下量化其性能。两种提出的TLE癫痫发作机制以不同程度和组合实施:通过苔藓纤维发芽的GCs反复兴奋和增加PP输入。虽然增加PP强度只会逐渐降低模式分离,但已经轻微升高的发芽会急剧(非线性)损害模式分离。在大多数测试的过度兴奋网络中,漏电的GCs改善了模式分离。然而,在一些具有全或无癫痫发作行为的发芽情况下,无论有无漏电的GCs,模式分离都会被禁用。在非线性损伤的轻度发芽(和PP增加)区域,漏电的GCs在恢复模式分离性能方面特别有效。这些结果与以下假设一致,即实验观察到的GCs内在重新缩放有助于维持DG网络的生理功能。

相似文献

[1]
Intrinsic rescaling of granule cells restores pattern separation ability of a dentate gyrus network model during epileptic hyperexcitability.

Hippocampus. 2015-3

[2]
Mossy fiber sprouting interacts with sodium channel mutations to increase dentate gyrus excitability.

Epilepsia. 2009-8-13

[3]
Role of mossy fiber sprouting and mossy cell loss in hyperexcitability: a network model of the dentate gyrus incorporating cell types and axonal topography.

J Neurophysiol. 2005-1

[4]
Kv4.1, a Key Ion Channel For Low Frequency Firing of Dentate Granule Cells, Is Crucial for Pattern Separation.

J Neurosci. 2020-2-11

[5]
Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin.

Epilepsia. 2013-4-8

[6]
Epileptogenesis in the dentate gyrus: a critical perspective.

Prog Brain Res. 2007

[7]
Calcium permeable AMPA receptor-dependent long lasting plasticity of intrinsic excitability in fast spiking interneurons of the dentate gyrus decreases inhibition in the granule cell layer.

Hippocampus. 2015-3

[8]
Corruption of the dentate gyrus by "dominant" granule cells: Implications for dentate gyrus function in health and disease.

Neurobiol Learn Mem. 2016-3

[9]
Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo.

Hippocampus. 2009-7

[10]
A role for hilar cells in pattern separation in the dentate gyrus: a computational approach.

Hippocampus. 2009-4

引用本文的文献

[1]
Pre- and Post-synaptic Mechanisms of Neuronal Inhibition Assessed Through Biochemically Detailed Modeling of GABA Receptor Signaling.

J Neurosci. 2025-9-3

[2]
Excitatory synaptic integration mechanism of three types of granule cells in the dentate gyrus.

Cogn Neurodyn. 2025-12

[3]
Adult neurogenesis in the hippocampal dentate gyrus affects sparsely synchronized rhythms, associated with pattern separation and integration.

Cogn Neurodyn. 2024-10

[4]
An Information-Geometric Formulation of Pattern Separation and Evaluation of Existing Indices.

Entropy (Basel). 2024-8-29

[5]
Effect of adult-born immature granule cells on pattern separation in the hippocampal dentate gyrus.

Cogn Neurodyn. 2024-8

[6]
Robust and consistent measures of pattern separation based on information theory and demonstrated in the dentate gyrus.

PLoS Comput Biol. 2024-2

[7]
Early deficits in dentate circuit and behavioral pattern separation after concussive brain injury.

Exp Neurol. 2023-12

[8]
Disynaptic effect of hilar cells on pattern separation in a spiking neural network of hippocampal dentate gyrus.

Cogn Neurodyn. 2022-12

[9]
Progression in Time of Dentate Gyrus Granule Cell Layer Widening due to Excitotoxicity Occurs along In Vivo LTP Reinstatement and Contextual Fear Memory Recovery.

Neural Plast. 2022

[10]
A critical evaluation of dynamical systems models of bipolar disorder.

Transl Psychiatry. 2022-9-28

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索