Lopez Gabriela C, Van Camp Louis D, Kovaleski Ryan F, Schaid Michael D, Sherathiya Venus N, Cox Julia M, Lerner Talia N
Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Northwestern University Interdepartmental Neuroscience Program (NUIN), Evanston, IL 60208, USA.
Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Curr Biol. 2025 May 19;35(10):2433-2443.e5. doi: 10.1016/j.cub.2025.04.006. Epub 2025 Apr 22.
Avoidance learning-learning to avoid bad outcomes-is an essential survival behavior. Dopamine signals are widely observed in response to aversive stimuli, indicating they could play a role in learning about how to avoid these stimuli. However, it is unclear what computations dopamine signals perform to support avoidance learning. Furthermore, substantial heterogeneity in dopamine responses to aversive stimuli has been observed across nucleus accumbens (NAc) subregions. To understand how heterogeneous dopamine responses to aversive stimuli contribute to avoidance learning, we recorded NAc core (Core) and NAc ventromedial shell (vmShell) dopamine during a task in which mice could avoid a footshock punishment by moving to the opposite side of a 2-chamber apparatus during a 5-s warning cue. Both signals evolved substantially-but differently-with learning. We found that Core and vmShell dopamine signals responded oppositely to shocks at the beginning of training and oppositely to warning cues as cue-shock associations developed in mid-training. Core dopamine responses strengthen with learning and are especially evident during expert performance. vmShell dopamine responses to cues and shocks were present during early learning but were not sustained during expert performance. Our data support a model in which Core dopamine encodes prediction errors that guide the consolidation of avoidance learning, while vmShell dopamine guides initial cue-shock associations by signaling aversive salience.
回避学习——即学会避免不良后果——是一种基本的生存行为。多巴胺信号在对厌恶刺激的反应中被广泛观察到,这表明它们可能在学习如何避免这些刺激方面发挥作用。然而,尚不清楚多巴胺信号执行何种计算来支持回避学习。此外,在伏隔核(NAc)各亚区域中,已观察到多巴胺对厌恶刺激的反应存在显著异质性。为了了解多巴胺对厌恶刺激的异质性反应如何促进回避学习,我们在一项任务中记录了NAc核心区(Core)和NAc腹内侧壳区(vmShell)的多巴胺活动,在此任务中,小鼠可以在5秒的警告提示期间移动到双室装置的另一侧,从而避免足部电击惩罚。随着学习的进行,这两种信号都发生了显著但不同的变化。我们发现,在训练开始时,Core和vmShell多巴胺信号对电击的反应相反,而在训练中期随着线索-电击关联的形成,它们对警告提示的反应相反。Core多巴胺反应随着学习而增强,在专家表现期间尤为明显。vmShell多巴胺对提示和电击的反应在早期学习期间存在,但在专家表现期间并未持续。我们的数据支持这样一种模型,即Core多巴胺编码预测误差,指导回避学习的巩固,而vmShell多巴胺通过发出厌恶显著性信号来指导初始线索-电击关联。