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皮质纹状体对食欲性巴甫洛夫条件反应的抑制。

Corticostriatal Suppression of Appetitive Pavlovian Conditioned Responding.

机构信息

Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec H4B 1R6, Canada

Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec H4B 1R6, Canada.

出版信息

J Neurosci. 2022 Feb 2;42(5):834-849. doi: 10.1523/JNEUROSCI.1664-21.2021. Epub 2021 Dec 8.

Abstract

The capacity to suppress learned responses is essential for animals to adapt in dynamic environments. Extinction is a process by which animals learn to suppress conditioned responding when an expected outcome is omitted. The infralimbic (IL) cortex to nucleus accumbens shell (NAcS) neural circuit is implicated in suppressing conditioned responding after extinction, especially in the context of operant cocaine-seeking behavior. However, the role of the IL-to-NAcS neural circuit in the extinction of responding to appetitive Pavlovian cues is unknown, and the psychological mechanisms involved in response suppression following extinction are unclear. We trained male Long Evans rats to associate a 10 s auditory conditioned stimulus (CS; 14 trials per session) with a sucrose unconditioned stimulus (US; 0.2 ml per CS) in a specific context, and then following extinction in a different context, precipitated a renewal of CS responding by presenting the CS alone in the original Pavlovian conditioning context. Unilateral, optogenetic stimulation of the IL-to-NAcS circuit selectively during CS trials suppressed renewal. In a separate experiment, IL-to-NAcS stimulation suppressed CS responding regardless of prior extinction and impaired extinction retrieval. Finally, IL-to-NAcS stimulation during the CS did not suppress the acquisition of Pavlovian conditioning but was required for the subsequent expression of CS responding. These results are consistent with multiple studies showing that the IL-to-NAcS neural circuit is involved in the suppression of operant cocaine-seeking, extending these findings to appetitive Pavlovian cues. The suppression of appetitive Pavlovian responding following IL-to-NAcS circuit stimulation, however, does not appear to be an extinction-dependent process. Extinction is a form of inhibitory learning through which animals learn to suppress conditioned responding in the face of nonreinforcement. We investigated the role of the IL cortex inputs to the NAcS in the extinction of responding to appetitive Pavlovian cues and the psychological mechanisms involved in response suppression following extinction. Using optogenetics, we found that stimulating the IL-to-NAcS neural circuit suppressed context-induced renewal of conditioned responding after extinction. In a separate experiment, stimulating the IL-to-NAcS circuit suppressed conditioned responding in an extinction-independent manner. These findings can be used by future research aimed at understanding how corticostriatal circuits contribute to behavioral flexibility and mental disorders that involve the suppression of learned behaviors.

摘要

抑制习得反应的能力对于动物在动态环境中适应至关重要。消退是一种动物在预期结果缺失时学习抑制条件反应的过程。额下皮质(IL)到伏隔核壳(NAcS)的神经回路参与抑制消退后的条件反应,尤其是在操作性可卡因寻求行为的背景下。然而,IL 到 NAcS 神经回路在消退后对奖赏性巴甫洛夫线索的反应抑制中的作用尚不清楚,并且消退后涉及的反应抑制的心理机制尚不清楚。我们训练雄性长耳大仓鼠将 10 秒听觉条件刺激(CS;每个会话 14 次试验)与蔗糖非条件刺激(US;每次 CS 为 0.2ml)相关联,然后在不同的背景下进行消退,单独呈现 CS 在原始巴甫洛夫条件作用的背景下引发 CS 反应的恢复。在 CS 试验期间,单侧光遗传学刺激 IL 到 NAcS 回路选择性地抑制了恢复。在另一个实验中,IL 到 NAcS 的刺激抑制了 CS 的反应,而不论先前的消退如何,并损害了消退的检索。最后,IL 到 NAcS 的刺激在 CS 期间没有抑制巴甫洛夫条件作用的获得,但对于 CS 反应的随后表达是必需的。这些结果与多项研究一致,表明 IL 到 NAcS 神经回路参与抑制操作性可卡因寻求,将这些发现扩展到奖赏性巴甫洛夫线索。然而,IL 到 NAcS 回路刺激后的奖赏性巴甫洛夫反应的抑制似乎不是一种依赖于消退的过程。消退是一种抑制性学习形式,通过这种学习,动物学会在没有强化的情况下抑制条件反应。我们研究了 IL 皮质对 NAcS 的输入在消退后对奖赏性巴甫洛夫线索的反应抑制中的作用,以及消退后涉及的反应抑制的心理机制。使用光遗传学,我们发现刺激 IL 到 NAcS 神经回路抑制了消退后的条件反应的上下文诱导恢复。在另一个实验中,刺激 IL 到 NAcS 回路以与消退无关的方式抑制了条件反应。这些发现可被未来旨在理解皮质纹状体回路如何促进行为灵活性和涉及抑制习得行为的精神障碍的研究利用。

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