Computational modeling of GABAA receptor-mediated paired-pulse inhibition in the dentate gyrus
Computational modeling of GABAA receptor-mediated paired-pulse inhibition in the dentate gyrus
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DOI：
10.1007/s10827-010-0214-y
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发表时间：
2010-12-01
影响因子：
1.2
通讯作者：
Schwarzacher, Stephan W.
中科院分区：
文献类型：
--
作者：
Jedlicka, Peter;Deller, Thomas;Schwarzacher, Stephan W.
配对脉冲抑制（PPI）的细胞外场记录中观察到的群体尖峰被广泛用作海马网络抑制的读出。PPI反映了GABA（A）受体介导的通过局部中间神经元对主神经元的抑制。然而，由于其多突触的性质，很难分配PPI的变化精确的突触机制。在这里，我们使用一个详细的齿状回网络模型来模拟颗粒细胞动作电位的PPI，并分析其网络特性。我们的计算分析表明，PPI的结果主要是从结合体周前馈和反馈抑制颗粒细胞的篮细胞。篮状细胞介导的前馈抑制似乎是PPI的最重要来源。我们的模拟表明，PPI依赖于体细胞比树突状抑制颗粒细胞。此外，PPI受GABA（A）逆转电位（E-GABA）变化和颗粒细胞内在兴奋性改变的调节。总之，计算机建模提供了一个有用的工具，用于确定成对脉冲场电位响应中突触和内在细胞机制的作用。
Paired-pulse inhibition (PPI) of the population spike observed in extracellular field recordings is widely used as a read-out of hippocampal network inhibition. PPI reflects GABA(A) receptor-mediated inhibition of principal neurons through local interneurons. However, because of its polysynaptic nature, it is difficult to assign PPI changes to precise synaptic mechanisms. Here we used a detailed network model of the dentate gyrus to simulate PPI of granule cell action potentials and analyze its network properties. Our computational analysis indicates that PPI results mainly from a combination of perisomatic feed-forward and feedback inhibition of granule cells by basket cells. Feed-forward inhibition mediated by basket cells appeared to be the most significant source of PPI. Our simulations suggest that PPI depends more on somatic than on dendritic inhibition of granule cells. Furthermore, PPI was modulated by changes in GABA(A) reversal potential (E-GABA) and by alterations in intrinsic excitability of granule cells. In summary, computer modeling provides a useful tool for determining the role of synaptic and intrinsic cellular mechanisms in paired-pulse field potential responses.