Acute Aversive Stimuli Rapidly Increase the Activity of Ventral Tegmental Area Dopamine Neurons in Awake Mice

Acute Aversive Stimuli Rapidly Increase the Activity of Ventral Tegmental Area Dopamine Neurons in Awake Mice
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DOI:
10.1016/j.neuroscience.2018.06.027
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发表时间:
2018-08-21
期刊:
影响因子:
3.3
通讯作者:
Kuwaki, Tomoyuki
Kuwaki, Tomoyuki
中科院分区:
医学3区
文献类型:
--
作者:
Moriya, Shunpei;Yamashita, Akira;Kuwaki, Tomoyuki

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腹侧被盖区(VTA)是脑多巴胺能系统的起源之一,参与调节多种生理功能,如疼痛处理和动机。在这项研究中,我们利用纤维光度系统,专门调查多巴胺神经元的活动,在腹侧被盖区使用多巴胺转运蛋白启动子驱动的Cre重组酶表达小鼠和位点特异性感染的腺相关病毒携带的FLEX G-CaMP 6基因。正如预期的那样,G-CaMP 6的表达仅限于腹侧被盖区多巴胺神经元。我们记录了G-CaMP 6绿色荧光信号,这反映了多巴胺能神经元的活动,在清醒的小鼠暴露于夹尾,超声波,捕食者的气味,和一个男性入侵者的小鼠。这些刺激导致腹侧被盖区多巴胺神经元活性的快速和短暂的增加,而温和的尾部触摸和空盒子的出现的对照刺激没有引起任何变化。此外,在VTA多巴胺神经元中表达hrGFP而不是G-CaMP 6的对照动物中,任何这些刺激都没有改变荧光强度。我们的数据清楚地表明,急性厌恶刺激迅速增加腹侧被盖区多巴胺神经元的活动,从而表明一个显着处理的作用。(C)2018年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The ventral tegmental area (VTA) is one of the origins of the brain dopaminergic system and is involved in regulating various physiological functions such as pain processing and motivation. In this study, we utilized a fiber photometry system to specifically investigate the activity of dopamine neurons in the VTA using dopamine transporter promoter-driven Cre recombinase-expressing mice and site-specific infection of adeno-associated virus carrying the FLEX G-CaMP6 gene. As expected, expression of G-CaMP6 was restricted to VTA dopamine neurons. We recorded G-CaMP6 green fluorescent signal, which reflected dopaminergic neuronal activity, in awake mice exposed to tail pinch, ultrasonic sound, predator odor, and a male intruder mouse. These stimuli resulted in a rapid and short-lasting increase in the activity of VTA dopamine neurons while the control stimuli of a gentle tail touch and appearance of empty box did not induce any changes. In addition, fluorescence intensity was not changed by any of these stimuli in the control animals expressing hrGFP instead of G-CaMP6 in VTA dopamine neurons. Our data clearly show that acute aversive stimuli rapidly increase the activity of VTA dopamine neurons and thus suggest a salience-processing role. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.