Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse.

Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse.
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DOI:
10.1016/j.heares.2016.10.017
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发表时间:
2017-02
期刊:
影响因子:
2.8
通讯作者:
Portfors CV
Portfors CV
中科院分区:
医学1区
文献类型:
--
作者:
Felix RA 2nd;Elde CJ;Nevue AA;Portfors CV

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神经化学物质血清素(5-羟色胺,5-HT)参与各种行为功能,包括唤醒,奖励和注意力,并在几种复杂的大脑疾病中发挥作用。在听觉系统中,5-HT纤维支配许多皮层下核团,但几乎所有这些领域的5-HT的调节作用仍然知之甚少。在这项研究中,我们研究了耳蜗背核(DCN)神经元的放电活动后,5-羟色胺的离子导入应用。DCN是听觉通路中的早期部位,其接收来自中缝核的致密5-HT纤维输入,并且已经涉及以神经元过度兴奋为标志的听觉障碍的产生。从清醒小鼠DCN的记录表明,5-HT的离子电渗应用的尖峰频率,尖峰时间,和诱发尖峰阈值的异质性影响。我们发现56%的神经元在5-HT输送期间峰发放率增加,而22%的神经元峰发放率下降,其余神经元没有变化。这些变化与自发性和诱发性尖峰放电相似,通常伴有尖峰时间的变化。尖峰的增加与较低的第一个尖峰潜伏期和抖动,而减少尖峰一般有相反的影响尖峰时间。与对照条件相比,5-HT应用导致尖峰增加的情况下也表现出较低的阈值,而尖峰减少的情况下没有阈值变化。我们还发现5-HT 2受体亚型可能在介导兴奋性增加中起作用。我们的研究结果表明,5-HT可以调节清醒的动物的DCN的活动,它主要作用于增加神经元的兴奋性,在其他听觉区域,它在很大程度上具有抑制作用。5-HT对DCN功能的调节对正常听力和听力障碍状态下的听觉处理都有影响。
The neurochemical serotonin (5-hydroxytryptamine, 5-HT) is involved in a variety of behavioral functions including arousal, reward, and attention, and has a role in several complex disorders of the brain. In the auditory system, 5-HT fibers innervate a number of subcortical nuclei, yet the modulatory role of 5-HT in nearly all of these areas remains poorly understood. In this study, we examined spiking activity of neurons in the dorsal cochlear nucleus (DCN) following iontophoretic application of 5-HT. The DCN is an early site in the auditory pathway that receives dense 5-HT fiber input from the raphe nuclei and has been implicated in the generation of auditory disorders marked by neuronal hyperexcitability. Recordings from the DCN in awake mice demonstrated that iontophoretic application of 5-HT had heterogeneous effects on spiking rate, spike timing, and evoked spiking threshold. We found that 56% of neurons exhibited increases in spiking rate during 5-HT delivery, while 22% had decreases in rate and the remaining neurons had no change. These changes were similar for spontaneous and evoked spiking and were typically accompanied by changes in spike timing. Spiking increases were associated with lower first spike latencies and jitter, while decreases in spiking generally had opposing effects on spike timing. Cases in which 5-HT application resulted in increased spiking also exhibited lower thresholds compared to the control condition, while cases of decreased spiking had no threshold change. We also found that the 5-HT2 receptor subtype likely has a role in mediating increased excitability. Our results demonstrate that 5-HT can modulate activity in the DCN of awake animals and that it primarily acts to increase neuronal excitability, in contrast to other auditory regions where it largely has a suppressive role. Modulation of DCN function by 5-HT has implications for auditory processing in both normal hearing and disordered states.