Adjeroud Najia, Yagüe Sara, Yu-Taeger Libo, Bozon Bruno, Leblanc-Veyrac Pascale, Riess Olaf, Allain Philippe, Nguyen Huu Phuc, Doyère Valérie, El Massioui Nicole
Paris-Saclay Institute of Neuroscience, UMR 9197, Université Paris-Sud, Orsay F-91405, France; CNRS, Orsay F-91405, France; CHU Angers, Neuropsychological Unit, Department of Neurology, Angers, France.
Paris-Saclay Institute of Neuroscience, UMR 9197, Université Paris-Sud, Orsay F-91405, France; CNRS, Orsay F-91405, France.
Neurobiol Learn Mem. 2015 Nov;125:249-57. doi: 10.1016/j.nlm.2015.10.003. Epub 2015 Oct 14.
Executive dysfunction and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder genetically characterized by expanded CAG repeats in the HTT gene. Using the BACHD rat model of HD (97 CAG-CAA repeats), the present research seeks to characterize the progressive emergence of decision-making impairments in a rat version of the Iowa Gambling Task (RGT) and the impact of emotional modulation, whether positive or negative, on choice behavior. The choice efficiency shown both by WT rats (independent of their age) and the youngest BACHD rats (2 and 8months old) evidenced that they are able to integrate outcomes of past decisions to determine expected reward values for each option. However, 18months old BACHD rats made fewer choices during the RGT session and were less efficient in choosing advantageous options than younger animals. Presenting either chocolate pellets or electrical footshocks half-way through a second RGT session reduced exploratory activity (inefficient nose-poking) and choices with a weaker effect on BACHD animals than on WT. Choice efficiency was left intact in transgenic rats. Our results bring new knowledge on executive impairments and impact of emotional state on decision-making at different stages of the disease, increasing the face-validity of the BACHD rat model.
执行功能障碍和精神症状是亨廷顿舞蹈症(HD)的标志,HD是一种神经退行性疾病,其遗传特征是HTT基因中的CAG重复序列扩增。本研究使用HD的BACHD大鼠模型(97个CAG - CAA重复序列),旨在描述大鼠版爱荷华赌博任务(RGT)中决策障碍的逐渐出现,以及积极或消极情绪调节对选择行为的影响。野生型大鼠(无论年龄)和最年幼的BACHD大鼠(2个月和8个月大)所表现出的选择效率证明,它们能够整合过去决策的结果,以确定每个选项的预期奖励值。然而,18个月大的BACHD大鼠在RGT实验过程中做出的选择较少,并且与年幼动物相比,在选择有利选项方面效率较低。在第二个RGT实验过程中中途呈现巧克力颗粒或电击会减少探索活动(无效的探鼻行为)和选择,对BACHD动物的影响比对野生型动物的影响更小。转基因大鼠的选择效率保持不变。我们的研究结果为疾病不同阶段的执行功能障碍以及情绪状态对决策的影响带来了新知识,提高了BACHD大鼠模型的表面效度。