Abstract：
A growing body of literature indicates that mediated learning techniques have specific utility for tapping into reality testing in animal models of neuropsychiatric illness. In particular, recent work has shown that animal models that recapitulate various endophenotypes of schizophrenia are particularly vulnerable to impairments in reality testing when undergoing mediated learning. Multiple studies have indicated that these effects are dopamine receptor 2-dependent and correlated with aberrant insular cortex (IC) activity. However, until now, the connection between dopamine and the IC had not been investigated. Here, we utilized a novel intersectional approach to label mesencephalic dopamine cells that specifically project to the insular cortex in both wild-type controls and transgenic mice expressing the dominant-negative form of the Disrupted-in-Schizophrenia-1 (DISC-1) gene. Using these techniques, we identified a population of cells that project from the ventral tegmental area (VTA) to the IC. Afterward, we conducted multiple studies to test the necessity of this circuit in behaviors ranging from gustatory detection to the maintenance of effort and, finally, mediated performance. Our results indicate that perturbations of the DISC-1 genetic locus lead to a reduction in the number of cells in the VTA → IC circuit. Behaviorally, VTA → IC circuitry does not influence gustatory detection or motivation to acquire sucrose reward; however, inactivation of this circuit differentially suppresses Pavlovian approach behavior in wild-type and DISC-1 transgenic mice during mediated performance testing. Moreover, under these testing conditions, inactivation of this circuit predisposes wild-type (but not DISC-1) mice to display impaired reality testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
摘要：
越来越多的文献表明，介导的学习技术对于在神经精神疾病的动物模型中进行现实测试具有特殊的用途。特别是,最近的工作表明，在进行介导学习时，在现实测试中，概括精神分裂症各种内表型的动物模型特别容易受到损害。多项研究表明，这些作用是多巴胺受体2依赖性的，并与异常的岛叶皮质（IC）活性相关。然而,直到现在,多巴胺与IC之间的联系尚未得到研究.这里,在野生型对照和表达显性阴性型精神分裂症破裂-1(DISC-1)基因的转基因小鼠中,我们利用一种新的交叉方法标记了特异性投射到岛叶皮质的中脑多巴胺细胞.使用这些技术，我们确定了从腹侧被盖区（VTA）投射到IC的细胞群。之后,我们进行了多项研究，以测试这种电路在从味觉检测到维持努力的行为中的必要性，最后,中介绩效。我们的结果表明，DISC-1遗传基因座的扰动导致VTA→IC电路中细胞数量的减少。行为上,VTA→IC电路不会影响味觉检测或获得蔗糖奖励的动机；但是，在介导的性能测试过程中，该电路的失活会差异抑制野生型和DISC-1转基因小鼠的巴甫洛夫方法行为。此外，在这些测试条件下，该电路的失活使野生型（但不是DISC-1）小鼠显示受损的现实测试。（PsycInfo数据库记录（c）2024APA，保留所有权利)。
