白噪声(WN)是一种降低伏隔核(NAC)内多巴胺浓度的厌恶性刺激。(A)左:大鼠在实时场所厌恶测试(30分钟)中的示例轨迹,其中进入一个象限(阴影),该象限是在测试前随机确定的,导致90分贝的WN暴露。右:地点厌恶试验中对WN的厌恶程度被量化为在WN象限停留的时间显著减少(n = 10, 9.71±1.65,t(9) = 9.585, p<0.0001)。(B)左:第二组大鼠被放置在开阔的场地上,在第一阶段评估它们的偏好象限。在第二阶段,进入首选象限导致90分贝的WN暴露。右:当在此象限内给予WN时,大鼠在该象限内停留的时间显著减少(n = 15, No WN: 48.5±0.2474,90 dB: 7.983±0.3875,t(14) = 13.43, p<0.0001)。(C)左:第三组大鼠(n = 12)暴露在一个露天觅食任务中,在其中一个象限的网格地板棒之间放置食物球。进入网格层象限(阴影)导致在单独的会话中暴露0、70、80、90或96 dB的WN或3 kHz的音调。中:增加WN强度剂量依赖性地减少了大鼠在网格-地板象限内觅食的时间(χ2(5) = 27.6, p<0.0001),而音调并没有减少觅食(70 dB WN vs. 70 dB音调(#);T (10) = 2.389, p=0.0381)。 Right: the rats’ response to the different WN intensities and the tone was reliable across first and second sessions of exposure, where rats underwent exposure to all WN intensities and the tone in a first session, before exposure to each in a second session. (D) Left: all other experiments took place in operant boxes equipped with a food magazine, a multiple-tone generator (cue speaker), and a WN generator (WN speaker). Middle: semi-random presentations of 6 s WN bouts increased the locomotion speed of rats (cohort 4; n = 14) in an operant box during the WN epoch compared to pre-WN baseline (post-hoc Dunn’s test, t(13) = 7.059, p<0.0001). Right: in another cohort of rats (cohort 5; n = 13), we tested different WN intensities and found a main effect of intensity on locomotion speed (χ2(3) = 13.80, p=0.0032) and significant differences between 70 and 90 dB (p=0.005) and 70 and 96 dB (p=0.0143) (n=13). (E) Rats (n = 17) responded reliably with increased locomotion speed to WN across days. (F) Rats (cohort 6; n = 9) discern between different WN magnitudes in an operant choice task, where they had to choose between pressing a lever that resulted in a food-pellet delivery and a lever that resulted in a food-pellet delivery plus simultaneous 5 s of 0, 70, 90, or 96 dB of WN (pellet + WN; Friedman test, χ2(3) = 11.57, p=0.0003). (G) Left: example cresyl violet-stained brain slice depicting an electrolytic lesion in the NAC (outlined) at the tip of the fast-scan cyclic voltammetry (FSCV) electrode (vertical black line). Right: schematic overview of FSCV recording locations (blue dots) in the NAC (gray) of all animals. (H) Single-trial pseudocolor plot (top panel), dopamine trace (bottom panel), and cyclic voltammograms (inset in bottom panel) for representative, dopamine-specific current fluctuations recorded in NAC, 5 s before WN (dashed line), during 6 s of WN (gray bar), and 14 s after WN. Except for panel (H), data are mean ± SEM. *p<0.05, **p<0.01, ***p<0.001. Credit:eLife(2022)。DOI: 10.7554 / eLife.82711
现发表于eLife荷兰神经科学研究所(Netherlands Institute for Neuroscience)的一项新研究研究了多巴胺系统如何处理厌恶事件。博士生Jessica Goedhoop和组长Ingo Willuhn带领的团队将大鼠暴露在白噪音和预测白噪音的刺激中,同时测量大脑中多巴胺的释放。白噪音是老鼠不愉快的听觉刺激的一个众所周知的例子。