Balci Fuat, Day Mark, Rooney Aislinn, Brunner Dani
PsychoGenics Inc., Tarrytown, NY, USA.
Behav Neurosci. 2009 Dec;123(6):1353-8. doi: 10.1037/a0017650.
Huntington's disease is characterized by corticostriatal dysfunction and degeneration of the striatum with progressive loss of the medium spiny neurons. These circuits are important for instrumental responding, interval timing, and temporal control over motor output. We investigated the acquisition of timed operant responding in two R6/2 Huntington's Disease models, differing in CAG repeat length and genetic background (115 and 250 CAG repeats, and a mixed CBAxC57 or pure C57 background) and their corresponding wild type controls using the peak procedure. Both mouse lines exhibited similar response control deficits. In unreinforced peak trials, mice either did not learn to terminate an ongoing response past reinforcement time or required more trials to acquisition compared to the wild type mice. While transgenic and wild type mice did not exhibit differences in temporal accuracy, response curves were flatter in transgenic mice, suggesting decreased temporal control over operant responding. The results are discussed in terms of the neurobiology of interval timing, instrumental responding, and the neuropathology of HD and R6/2 mice.
亨廷顿舞蹈症的特征是皮质纹状体功能障碍和纹状体变性，伴有中等棘状神经元的逐渐丧失。这些神经回路对于工具性反应、间隔计时以及对运动输出的时间控制非常重要。我们使用峰值程序，研究了两种R6/2亨廷顿舞蹈症模型（CAG重复长度和遗传背景不同，分别为115和250个CAG重复，以及混合的CBAxC57或纯C57背景）及其相应野生型对照在定时操作性反应方面的习得情况。两种小鼠品系均表现出相似的反应控制缺陷。在无强化的峰值试验中，与野生型小鼠相比，这些小鼠要么没有学会在强化时间过去后终止正在进行的反应，要么需要更多试验才能习得。虽然转基因小鼠和野生型小鼠在时间准确性上没有差异，但转基因小鼠的反应曲线更平缓，这表明对操作性反应的时间控制有所下降。我们从间隔计时的神经生物学、工具性反应以及HD和R6/2小鼠的神经病理学角度对这些结果进行了讨论。
