Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons.
Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons.
复制标题
DOI：
10.1038/nature12330
复制
发表时间：
2013-08-22
期刊：
影响因子：
64.8
通讯作者：
Tsien RW
中科院分区：
文献类型：
--
作者：
Owen SF;Tuncdemir SN;Bader PL;Tirko NN;Fishell G;Tsien RW
催产素对神经调节的控制对社会、父母和压力相关的行为都是必不可少的。自闭症谱系障碍（ASD）与催产素水平缺乏和催产素受体（OXTR）的遗传改变有关。30年前，m<s:1> hlethaleret al.发现催产素增加了抑制性海马神经元的放电，但尚不清楚抑制作用的增强如何解释催产素改善大脑信息处理的能力。在哺乳动物海马中，我们描述了一种简单而强大的机制，即催产素在增强皮质信息传递的同时降低背景活动，从而大大提高信噪比。快速尖峰神经元间活动的增加不仅抑制了锥体细胞的自发放电，而且提高了尖峰传递的保真度和尖峰时间。使用依赖性抑制在快速尖峰神经元间-锥体细胞突触是必要的和充分的提高尖峰吞吐量。我们通过使用胆囊收缩素或通道视紫红质-2激活快速尖峰的中间神经元来展示这种新的电路机制的普遍性。这提供了一个深入了解如何扩散传递神经调节剂可以改善神经回路的性能，需要突触特异性和毫秒精度。
Neuromodulatory control by oxytocin is essential to a wide range of social,, parental and stress-related behaviours. Autism spectrum disorders (ASD) are associated with deficiencies in oxytocin levels and with genetic alterations of the oxytocin receptor (OXTR). Thirty years ago, Mühlethaleret al. found that oxytocin increases the firing of inhibitory hippocampal neurons, but it remains unclear how elevated inhibition could account for the ability of oxytocin to improve information processing in the brain. Here we describe in mammalian hippocampus a simple yet powerful mechanism by which oxytocin enhances cortical information transfer while simultaneously lowering background activity, thus greatly improving the signal-to-noise ratio. Increased fast-spiking interneuron activity not only suppresses spontaneous pyramidal cell firing, but also enhances the fidelity of spike transmission and sharpens spike timing. Use-dependent depression at the fast-spiking interneuron–pyramidal cell synapse is both necessary and sufficient for the enhanced spike throughput. We show the generality of this novel circuit mechanism by activation of fast-spiking interneurons with cholecystokinin or channelrhodopsin-2. This provides insight into how a diffusely delivered neuromodulator can improve the performance of neural circuitry that requires synapse specificity and millisecond precision.