Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus.
Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus.
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DOI：
10.3390/ijms22094507
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发表时间：
2021-04-26
影响因子：
5.6
通讯作者：
Syka J
中科院分区：
文献类型：
--
作者：
Chumak T;Tothova D;Filova I;Bures Z;Popelar J;Pavlinkova G;Syka J
LIM同源结构域转录因子ISL1在神经元发育和维持的不同方面是必不可少的。为了研究Isl1在听觉系统中的作用，我们建立了在Pax2启动子控制下表达Isl1的转基因小鼠(TG)。我们之前报告了这些转基因小鼠的听力和内耳、内侧橄榄耳蜗系统和听觉中脑的异常与年龄相关的进行性下降。在这项研究中，我们研究了Isl1过度表达如何影响下丘(IC)神经元的声音处理。我们记录了细胞外神经元的活动，并分析了IC神经元对宽带噪声、短声、纯音、双音刺激和调频声音的反应。我们发现，双音刺激对TG动物表现出较高的抑制作用；它们表现出更宽的动态范围，更低的自发放电率，更长的第一峰潜伏期，以及在对调频声音的加工中，表现出普遍的高频抑制。与野生型动物相比，与野生型动物相比，TG小鼠IC的功能改变伴随着Calretinin和Parvalprotein阳性神经元数量的减少，泡状GABA/甘氨酸转运体和Calbindin表达的增加。这些结果进一步表征了TG小鼠IC中的异常声音处理，并表明主要的变化发生在抑制侧。
The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.
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DOI：
10.1073/pnas.93.24.13870
发表时间：
1996-11-26
影响因子：
11.1
作者：
Favor, J;Sandulache, R;Schughart, K
通讯作者：
Schughart, K
影响因子：
3.1
作者：
Bureš Z;Pysanenko K;Lindovský J;Syka J
通讯作者：
Syka J
影响因子：
2.5
作者：
AITKIN, LM;KENYON, CE;PHILPOTT, P
通讯作者：
PHILPOTT, P
影响因子：
2.5
作者：
D'Angelo, WR;Sterbing, SJ;Kuwada, S
通讯作者：
Kuwada, S
影响因子：
2.7
作者：
Lin, Lizhu;Bu, Lei;Evans, Sylvia
通讯作者：
Evans, Sylvia