Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location
Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location
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DOI：
10.1113/jphysiol.2011.226233
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发表时间：
2012-07-01
影响因子：
5.5
通讯作者：
Burger, R. Michael
中科院分区：
文献类型：
--
作者：
Fischl, Matthew J.;Combs, T. Dalton;Burger, R. Michael
生物体利用耳间时间差异 (ITD) 来定位低频，其中内侧上橄榄 (MSO) 中的专门神经元计算声音到达每只耳朵的亚毫秒差异，该值随声音位置而系统地变化。尽管输入强度的变化很大，但这些神经元仍能在 1012 倍的声音强度范围内计算声音位置。突触增益的调节已被建议作为维持准确的 ITD 处理的机制。在这里，我们发现 GABAB 受体的激活会抑制 MSO 的兴奋性和抑制性输入，并改变抑制性突触电流的动力学。使用体外生理方法和计算模型，我们表明 GABAB 受体激活的调节有助于 MSO 神经元的空间调谐。这些结果有助于理解神经元如何在广泛变化的输入条件下保持计算稳定性。摘要 耳间时间差异（ITD）是低频声音刺激定位的主要线索。 ITD 是通过哺乳动物内侧上橄榄 (MSO) 中的巧合检测神经元计算的。先前的几项研究表明，随着刺激强度的增加，控制突触增益对于维持 ITD 选择性至关重要。使用出生后第 7 天至 24 天 (P7P24) 蒙古沙鼠的急性脑切片，我们证实 GABAB 受体的激活降低了 MSO 的兴奋性和抑制性突触电流的幅度，此外，表明成熟动物中 IPSC 的衰减动力学减慢。在重复刺激过程中，GABAB 受体的激活减少了观察到的抑郁程度，而 PSC 抑制和动力学减慢得以维持。此外，我们使用生理学和建模方法来测试 GABAB 激活对 MSO 神经元中 ITD 编码的潜在影响。对 MSO 神经元进行电流钳记录，同时使用体外模拟 ITD 的脉冲序列对药理学上隔离的兴奋性输入进行双边刺激。 MSO 神经元对双侧延迟表现出很强的选择性。 GABAB 激动剂和拮抗剂的应用表明，GABAB 对突触输入的调节可以提高 ITD 选择性。我们在计算模型中确认并扩展了这些结果，该模型允许独立操纵每个 GABAB 依赖性效应。建模表明，GABAB 受体对突触输入的幅度和动力学的调节可以提高 ITD 计算的精度。我们的研究表明，GABAB 受体对突触输入的体内调节可能有助于保持 ITD 在各种刺激条件下的选择性。
Key points Organisms localise low frequencies using interaural time disparities (ITDs) in which specialized neurones in the medial superior olive (MSO) compute submillisecond differences in arrival time of sounds to each ear, a value that varies systematically with sound location. These neurones compute sound location over a 1012 fold range in sound intensities, despite large intensity-dependent changes in input strength. Modulation of synaptic gain has been suggested as a mechanism to maintain accurate ITD processing. Here we show that activation of GABAB receptors suppresses both the excitatory and inhibitory inputs to the MSO and alters the kinetics of inhibitory synaptic currents. Using in vitro physiological methods and computational modelling, we show that the modulation by GABAB receptor activation contributes to spatial tuning of MSO neurones. These results contribute to the understanding of how neurones maintain computational stability under widely varying input conditions. Abstract Interaural time disparities (ITDs) are the primary cues for localisation of low-frequency sound stimuli. ITDs are computed by coincidence-detecting neurones in the medial superior olive (MSO) in mammals. Several previous studies suggest that control of synaptic gain is essential for maintaining ITD selectivity as stimulus intensity increases. Using acute brain slices from postnatal day 7 to 24 (P7P24) Mongolian gerbils, we confirm that activation of GABAB receptors reduces the amplitude of excitatory and inhibitory synaptic currents to the MSO and, moreover, show that the decay kinetics of IPSCs are slowed in mature animals. During repetitive stimuli, activation of GABAB receptors reduced the amount of depression observed, while PSC suppression and the slowed kinetics were maintained. Additionally, we used physiological and modelling approaches to test the potential impact of GABAB activation on ITD encoding in MSO neurones. Current clamp recordings from MSO neurones were made while pharmacologically isolated excitatory inputs were bilaterally stimulated using pulse trains that simulate ITDs in vitro. MSO neurones showed strong selectivity for bilateral delays. Application of both GABAB agonists and antagonists demonstrate that GABAB modulation of synaptic input can sharpen ITD selectivity. We confirmed and extended these results in a computational model that allowed for independent manipulation of each GABAB-dependent effect. Modelling suggests that modulation of both amplitude and kinetics of synaptic inputs by GABAB receptors can improve precision of ITD computation. Our studies suggest that in vivo modulation of synaptic input by GABAB receptors may act to preserve ITD selectivity across various stimulus conditions.