Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum.
Devaluation of response-produced safety signals reveals circuits for goal-directed versus habitual avoidance in dorsal striatum.
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反应产生的安全信号的贬值揭示了背侧纹状体中目标导向与习惯性回避的回路。
DOI：
10.1101/2024.02.07.579321
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Cain,ChristopherK
中科院分区：
文献类型：
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作者：
Sears,RobertM;Andrade,ErikaC;Samels,ShannaB;Laughlin,LindsayC;Moloney,DanielleM;Wilson,DonaldA;Alwood,MatthewR;Moscarello,JustinM;Cain,ChristopherK
主动回避反应（AR）是防止伤害的工具性行为。适应性AR可能有助于积极应对，而适应不良的回避习惯与焦虑和强迫症有关。AR学习机制仍然难以捉摸，因为成功的回避试验没有产生明显的结果。我们在大鼠中使用了一种新的结果贬值程序，以表明AR被反应产生的反馈（FB）线索积极加强，这些线索在训练过程中发展成为安全信号。男性敏感FB贬值后，适度的训练，但不过度训练，符合从目标导向的过渡到习惯性回避。使用化学遗传学和FB贬值，我们还表明，目标导向与习惯性AR依赖于背内侧与背外侧纹状体，这表明回避和奖励工具行为的机制之间存在显着的重叠。女性是不敏感的FB贬值由于显着的上下文依赖性的反调节。然而，降低AR-FB应急表明，两种性别都依赖于安全信号来执行目标导向的AR。
Active avoidance responses (ARs) are instrumental behaviors that prevent harm. Adaptive ARs may contribute to active coping, whereas maladaptive avoidance habits are implicated in anxiety and obsessive-compulsive disorders. The AR learning mechanism has remained elusive, as successful avoidance trials produce no obvious reinforcer. We used a novel outcome-devaluation procedure in rats to show that ARs are positively reinforced by response-produced feedback (FB) cues that develop into safety signals during training. Males were sensitive to FB-devaluation after moderate training, but not overtraining, consistent with a transition from goal-directed to habitual avoidance. Using chemogenetics and FB-devaluation, we also show that goal-directed vs. habitual ARs depend on dorsomedial vs. dorsolateral striatum, suggesting a significant overlap between the mechanisms of avoidance and rewarded instrumental behavior. Females were insensitive to FB-devaluation due to a remarkable context-dependence of counterconditioning. However, degrading the AR-FB contingency suggests that both sexes rely on safety signals to perform goal-directed ARs.