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雄性大鼠外侧眶额皮质失活后过预期学习的持续破坏。

Persistent disruption of overexpectation learning after inactivation of the lateral orbitofrontal cortex in male rats.

机构信息

Center for Studies in Behavioural Neurobiology, Department of Psychology, Concordia University, Montreal, QC, Canada.

Department of Psychology, Brooklyn College of the City University of New York, Brooklyn, NY, USA.

出版信息

Psychopharmacology (Berl). 2023 Mar;240(3):501-511. doi: 10.1007/s00213-022-06198-2. Epub 2022 Aug 6.

Abstract

RATIONALE AND OBJECTIVE

Learning to inhibit acquired fear responses is fundamental to adaptive behavior. Two procedures that support such learning are extinction and overexpectation. In extinction, an expected outcome is omitted, whereas in overexpectation two individually trained cues are presented in compound to induce an expectation of a greater outcome than that delivered. Previously, we showed that inactivation of the lateral orbitofrontal cortex (lOFC) in experimentally naïve male rats causes a mild impairment in extinction learning but a profound one in overexpectation. The mild extinction impairment was also transient; that is, it was absent in a cohort of rats that had prior history of inhibitory training (overexpectation, extinction) and their associated controls. This raised the question whether lOFC involvement in overexpectation could likewise be attenuated by prior experience.

METHODS

Using a muscimol/baclofen cocktail, we inactivated the lOFC during overexpectation training in rats with prior associative learning history (extinction, overexpectation, control) and examined its contribution to reducing learned fear.

RESULTS

Inactivating the lOFC during compound training in overexpectation persistently disrupted fear reduction on test in naïve rats and regardless of prior experience. Additionally, we confirm that silencing the lOFC only resulted in a mild impairment in extinction learning in naïve rats.

CONCLUSION

We show that prior associative learning experience did not mitigate the deficit in overexpectation caused by lOFC inactivation. Our findings emphasize the importance of this region for this particular form of fear reduction and broaden our understanding of the conditions in which the lOFC modulates behavioral inhibition.

摘要

原理与目的

习得性恐惧反应的抑制对于适应性行为至关重要。两种支持这种学习的程序是消退和过度预期。在消退中,省略了预期的结果,而在过度预期中,两个单独训练的线索同时呈现,以诱导对更大结果的期望。此前,我们发现实验性地使未接受过训练的雄性大鼠的外侧眶额皮层(lOFC)失活,会导致其在消退学习中轻度受损,但在过度预期中则会严重受损。这种轻度的消退损伤也是短暂的;也就是说,在一组先前接受过抑制性训练(过度预期、消退)及其相关对照的大鼠中,这种损伤是不存在的。这就提出了一个问题,即 lOFC 参与过度预期是否也可以通过先前的经验来减弱。

方法

使用毒蕈碱/巴氯芬鸡尾酒,我们在具有先前关联学习史(消退、过度预期、对照)的大鼠的过度预期训练期间使 lOFC 失活,并检查其对减少习得性恐惧的贡献。

结果

在过度预期训练中,在 lOFC 失活时,即使在没有经验的情况下,也会持续破坏大鼠的恐惧减轻。此外,我们证实,在没有经验的大鼠中,沉默 lOFC 只会导致消退学习的轻度损伤。

结论

我们表明,先前的关联学习经验并不能减轻 lOFC 失活引起的过度预期缺陷。我们的发现强调了该区域对于这种特殊形式的恐惧减轻的重要性,并拓宽了我们对 lOFC 调节行为抑制的条件的理解。

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