Unilateral caudate inactivation increases motor impulsivity in rhesus monkeys

Mark A.G. Eldridge , Maya C. Smith , Scott Hunter Oppler , Jonah E. Pearl , Jalene Y. Shim , Walter Lerchner , Barry J. Richmond
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Abstract

Impulsivity, the tendency to react quickly and without consideration of consequences, is correlated with asymmetry in the volume of the caudate nucleus in human patients. In this study, we sought to determine whether the induction of functional asymmetry in the caudate nucleus of monkeys would produce phenomenologically comparable behavior. We found that unilateral suppression of the ventral caudate nucleus increases impulsive behavior in rhesus monkeys. Impulsivity was modeled by the subjects’ inability to maintain hold of a touch-sensitive bar until presentation of an imperative signal. Two methods were used to suppress activity in the caudate region. First, muscimol was locally infused. Second, a viral construct expressing the hM4Di DREADD (designer receptor exclusively activated by designer drug) was injected at the same site. Clozapine N-oxide and deschloroclozapine activate the DREADD to suppress neuronal activity. Both methods of suppression, pharmacological and chemogenetic, increased the rate of early bar releases, a behavior we interpret to indicate impulsivity. Thus, we demonstrate a causal relationship between caudate asymmetry and impulsivity.

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单侧尾状核失活会增加恒河猴的运动冲动
冲动,即快速反应而不考虑后果的倾向,与人类患者尾状核体积的不对称有关。在这项研究中,我们试图确定猴子尾状核功能不对称的诱导是否会产生现象学上可比的行为。我们发现单侧抑制腹侧尾状核会增加恒河猴的冲动行为。冲动是通过受试者在出现命令信号之前无法保持触摸感应条来建模的。使用两种方法抑制尾状区的活性。首先,局部输注麝香醇。其次,在同一位点注射表达hM4Di DREADD(由设计药物专门激活的设计受体)的病毒构建体。氯氮平N-氧化物和去氯氯氮平激活DREADD以抑制神经元活性。药理学和化学遗传学的两种抑制方法都增加了早期bar释放的速率,我们将这种行为解释为冲动。因此,我们证明了尾状体不对称和冲动之间的因果关系。
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