Hippocampal Ripple Oscillations and Inhibition-First Network Models: Frequency Dynamics and Response to GABA Modulators
Hippocampal Ripple Oscillations and Inhibition-First Network Models: Frequency Dynamics and Response to GABA Modulators
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DOI：
10.1523/jneurosci.0188-17.2018
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发表时间：
2018-03-21
影响因子：
5.3
通讯作者：
Kempter, Richard
中科院分区：
文献类型：
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作者：
Donoso, Jose R.;Schmitz, Dietmar;Kempter, Richard
海马波纹与记忆巩固有关，但其产生的机制仍不清楚。依赖于CA 1区域的中间神经元网络的模型不同意中间神经元的主要兴奋来源：“直接”，通过从CA 3到CA 1提供前馈输入的Schaffer侧支，或“间接”，通过CA 1中的局部锥体细胞，这些细胞嵌入在复发性兴奋-抑制网络中。在这里，我们使用生理约束的计算模型的篮细胞网络，以研究它们如何响应不同的条件下的瞬态，嘈杂的激励。我们发现，直接激发中间神经元可以引起涟漪（140 - 220 Hz），表现出内波纹频率的适应性和频率不敏感的GABA调制器，如先前在体外实验中所示。此外，篮状细胞网络的间接激发使得能够在快γ范围（90 - 140 Hz）内表达频率调节，如在体内。在我们的模型中，intraripple频率调节的结果从一个滞后现象，在该现象中的频率响应不同的上升和下降阶段的瞬态激励。这种现象预示着最大振荡频率出现在激励峰值之前几毫秒。我们证实了这一预测的波纹在大脑切片从雄性小鼠。这些结果表明，涟漪和快速伽马事件产生的相同的interneuron网络，通过不同的兴奋性输入途径，这可能是由先前报道的篮状细胞和功能不同的锥体细胞在CA 1的亚群之间的intralaminar连接的偏见。总之，我们的研究结果统一了海马体中节律产生的竞争性抑制模型。
Hippocampal ripples are involved in memory consolidation, but the mechanisms underlying their generation remain unclear. Models relying on interneuron networks in the CA1 region disagree on the predominant source of excitation to interneurons: either "direct," via the Schaffer collaterals that provide feedforward input from CA3 to CA1, or " indirect," via the local pyramidal cells in CA1, which are embedded in a recurrent excitatory-inhibitory network. Here, we used physiologically constrained computational models of basket-cell networks to investigate how they respond to different conditions of transient, noisy excitation. We found that direct excitation of interneurons could evoke ripples (140 - 220 Hz) that exhibited intraripple frequency accommodation and were frequency-insensitive to GABA modulators, as previously shown in in vitro experiments. In addition, the indirect excitation of the basket-cell network enabled the expression of intraripple frequency accommodation in the fast-gamma range (90 - 140 Hz), as in vivo. In our model, intraripple frequency accommodation results from a hysteresis phenomenon in which the frequency responds differentially to the rising and descending phases of the transient excitation. Such a phenomenon predicts a maximum oscillation frequency occurring several milliseconds before the peak of excitation. We confirmed this prediction for ripples in brain slices from male mice. These results suggest that ripple and fast-gamma episodes are produced by the same interneuron network that is recruited via different excitatory input pathways, which could be supported by the previously reported intralaminar connectivity bias between basket cells and functionally distinct subpopulations of pyramidal cells in CA1. Together, our findings unify competing inhibition-first models of rhythm generation in the hippocampus.