PDF(Pubmed)
Abstract：
Habits are familiar behaviors triggered by cues, not outcome predictability, and are insensitive to changes in the environment. They are adaptive under many circumstances but can be considered antecedent to compulsions and intrusive thoughts that drive persistent, potentially maladaptive behavior. Whether compulsive-like and habit-like behaviors share neural substrates is still being determined. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences. We found that these mice demonstrate habitual response biases and compulsive-like grooming behavior that was reversible by fluoxetine and ketamine. They also suffer dendritic spine attrition on excitatory neurons in the orbitofrontal cortex (OFC). Nevertheless, synaptic melanocortin 4 receptor (MC4R), a factor implicated in compulsive behavior, is preserved, leading to the hypothesis that Mc4r+ OFC neurons may drive aberrant behaviors. Repeated chemogenetic stimulation of Mc4r+ OFC neurons triggered compulsive and not inflexible or habitual response biases in otherwise typical mice. Thus, Mc4r+ neurons within the OFC appear to drive compulsive-like behavior that is dissociable from habitual behavior. Understanding which neuron populations trigger distinct behaviors may advance efforts to mitigate harmful compulsions.
摘要：
习惯是由线索引发的熟悉行为，不是结果的可预测性，对环境的变化不敏感。它们在许多情况下都是适应性的，但可以被认为是强迫性和侵入性思维的前身，潜在的不适应行为。强迫性和习惯性行为是否共享神经底物仍在确定中。这里,我们研究了对行动后果不敏感的表现出不灵活的寻求奖励行为的小鼠。我们发现，这些小鼠表现出习惯性反应偏见和强迫性样修饰行为，氟西汀和氯胺酮是可逆的。它们还在眶额皮质（OFC）的兴奋性神经元上遭受树突脊柱磨损。然而，突触黑皮质素4受体（MC4R），与强迫行为有关的因素，保存,导致Mc4r+OFC神经元可能驱动异常行为的假设。Mc4rOFC神经元的重复化学遗传刺激在其他典型小鼠中触发了强迫性而不是不灵活或习惯性的反应偏差。因此，OFC中的Mc4r神经元似乎驱动了与习惯性行为无关的强迫性行为。了解哪些神经元群体会触发不同的行为可能会促进减轻有害强迫的努力。
