The effects of Eph-ephrin mutations on pre-pulse inhibition in mice.
The effects of Eph-ephrin mutations on pre-pulse inhibition in mice.
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DOI：
10.1016/j.physbeh.2014.05.044
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发表时间：
2014-08
影响因子：
2.9
通讯作者：
Gabriele L
中科院分区：
文献类型：
--
作者：
Liuzzo A;Gray L;Wallace M;Gabriele L
众所周知，Eph-ephrin 信号传导对于指导传入听觉通路中的地形投射非常重要，包括与下丘 (IC) 各个部分的连接。声惊吓反应（ASR）是哺乳动物由意外的强烈声惊吓刺激（ES）引起的可靠的反射性行为反应。它由包括 IC 在内的皮层下通路介导。 ASR 幅度可以使用受试者下方的加速计进行测量，并且可以通过在 ES 之前 5-300 毫秒呈现不太强烈、非令人吃惊的刺激来降低幅度。 ASR 中的这种反射性减量称为预脉冲抑制 (PPI)，表明听到了相对较软的预脉冲。 PPI 是哺乳动物的普遍特征。最近使用小鼠来研究这种反应，并揭示基因突变如何影响神经回路，从而影响 ASR 和 PPI。在本实验中，我们使用对照小鼠 (C57BL/6J)、EphA4 信号传导受损的小鼠 (EphA4lacZ/+、EphA4lacZ/lacZ) 和基因敲除肝配蛋白-B3 小鼠 (肝配蛋白-B3 +/-、−/−) 测量了 Eph-ephrin 突变的影响。对照和 EphA4lacZ/+ 菌株在 ES 之前 50 毫秒表现出强大的 PPI（ASR 衰减高达 75%），可抵消 70 dB SPL 背景噪声。在相同条件下，Ephrin-B3 敲除小鼠和 EphA4 纯合突变体的 PPI 仅有轻微显着性（分别下降 < 25% 和 < 33%）。 PPI 的下降凸显了肝配蛋白 B3 和 EphA4 相互作用在听觉行为回路排序中的重要性。因此，信号传导家族某些成员的不同突变会产生 PPI 的全方位变化，从最小到接近最大。这项技术可以很容易地应用于研究更广泛的突变中听力的其他方面。连同正在进行的神经解剖学研究，这使得可以仔细量化听觉解剖学、生理学和行为表型如何受到 Eph-ephrin 表达和功能变化的影响。
Eph-ephrin signaling is known to be important in directing topographic projections in the afferent auditory pathway, including connections to various subdivisions of the inferior colliculus (IC). The acoustic startle-response (ASR) is a reliable reflexive behavioral response in mammals elicited by an unexpected intense acoustic startle-eliciting stimulus (ES). It is mediated by a sub-cortical pathway that includes the IC. The ASR amplitude can be measured with an accelerometer under the subject and can be decreased in amplitude by presenting a less intense, non-startling stimulus 5–300 ms before the ES. This reflexive decrement in ASR is called pre-pulse inhibition (PPI) and indicates that the relatively soft pre-pulse was heard. PPI is a general trait among mammals. Mice have been used recently to study this response and to reveal how genetic mutations affect neural circuits and hence the ASR and PPI. In this experiment, we measured the effect of Eph-ephrin mutations using control mice (C57BL/6J), mice with compromised EphA4 signaling (EphA4lacZ/+, EphA4lacZ/lacZ), and knockout ephrin-B3 mice (ephrin-B3 +/−, −/−). Control and EphA4lacZ/+ strains showed robust PPI (up to 75% decrement in ASR) to an offset of a 70 dB SPL background noise at 50 ms before the ES. Ephrin-B3 knockout mice and EphA4 homozygous mutants were only marginally significant in PPI (< 25% decrement and <33% decrement, respectively) to the same conditions. This decrement in PPI highlights the importance of ephrin-B3 and EphA4 interactions in ordering auditory behavioral circuits. Thus, different mutations in certain members of the signaling family produce a full range of changes in PPI, from minimal to nearly maximal. This technique can be easily adapted to study other aspects of hearing in a wider range of mutations. Along with ongoing neuroanatomical studies, this allows careful quantification of how the auditory anatomical, physiological and now behavioral phenotype is affected by changes in Eph-ephrin expression and functionality.
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