The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice
The Attentional Set Shifting Task: A Measure of Cognitive Flexibility in Mice
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DOI：
10.3791/51944
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发表时间：
2015-02-01
影响因子：
1.2
通讯作者：
O'Connor, Jason C.
中科院分区：
文献类型：
--
作者：
Heisler, Jillian M.;Morales, Juan;O'Connor, Jason C.
认知障碍，特别是涉及前额叶皮质（PFC）内电路功能障碍的认知障碍，是许多神经精神和神经发育障碍的核心特征，包括抑郁症、创伤后应激障碍、精神分裂症和自闭症谱系障碍。认知功能缺陷也是最难成功治疗的症状领域，因为5-羟色胺再摄取抑制剂和三环类抗抑郁药的作用不大。功能性神经影像学研究和人类脑组织的尸检分析表明，PFC是这些疾病患者调节失调的主要区域。然而，用于评估这些缺陷的小鼠模型，可以很容易地操纵基因，并可以提供新的治疗途径的研究基础的临床前行为测定一直未得到充分利用。在这里，我们描述了适应的行为测定，注意力转移任务（AST），在小鼠中进行，以评估前额叶皮层介导的认知缺陷。AST期间行为的神经回路在人类、非人灵长类动物和啮齿类动物中高度保守，提供了出色的面部、结构和预测有效性。
Cognitive impairment, particularly involving dysfunction of circuitry within the prefrontal cortex (PFC), represents a core feature of many neuropsychiatric and neurodevelopmental disorders, including depression, post-traumatic stress disorder, schizophrenia and autism spectrum disorder. Deficits in cognitive function also represent the most difficult symptom domain to successfully treat, as serotonin reuptake inhibitors and tricyclic antidepressants have only modest effects. Functional neuroimaging studies and postmortem analysis of human brain tissue implicate the PFC as being a primary region of dysregulation in patients with these disorders. However, preclinical behavioral assays used to assess these deficits in mouse models which can be readily manipulated genetically and could provide the basis for studies of new treatment avenues have been underutilized. Here we describe the adaptation of a behavioral assay, the attentional set shifting task (AST), to be performed in mice to assess prefrontal cortex mediated cognitive deficits. The neural circuits underlying behavior during the AST are highly conserved across humans, nonhuman primates and rodents, providing excellent face, construct and predictive validity.