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注意缺陷多动障碍啮齿动物模型中的视觉加工改变

Altered visual processing in a rodent model of Attention-Deficit Hyperactivity Disorder.

作者信息

Brace L R, Kraev I, Rostron C L, Stewart M G, Overton P G, Dommett E J

机构信息

Department of Life, Health and Chemical Sciences, The Open University, Milton Keynes MK7 6AA, UK.

Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.

出版信息

Neuroscience. 2015 Sep 10;303:364-77. doi: 10.1016/j.neuroscience.2015.07.003. Epub 2015 Jul 9.

Abstract

A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR). We examined collicular-dependent orienting behavior, local field potential (LFP) and multiunit responses to visual stimuli in the anesthetized rat and morphological measures in the SHR in comparison to the Wistar Kyoto (WKY) and Wistar (WIS). We found that SHRs remain responsive to a repeated visual stimulus for more presentations than control strains and have a longer response duration. In addition, LFP and multiunit activity within the visually responsive superficial layers of the SC showed the SHR to have a hyper-responsive SC relative to control strains, which could not be explained by altered functioning of the retinocollicular pathway. Finally, examination of collicular volume, neuron and glia densities and glia:neuron ratio revealed that the SHR had a reduced ratio relative to the WKY which could explain the increased responsiveness. In conclusion, this study demonstrates strain-specific changes in the functioning and structure of the SC in the SHR, providing convergent evidence that the SC might be dysfunctional in ADHD.

摘要

注意力缺陷多动障碍(ADHD)的一个核心特征是注意力分散增加,这在包括人类在内的一系列物种中都与上丘(SC)有关。此外,现在越来越多的证据表明ADHD患者的上丘功能发生了改变,有人提出反应过度的上丘可能介导了ADHD的主要症状,包括注意力分散。在本研究中,我们对ADHD最常用且经过充分验证的动物模型——自发性高血压大鼠(SHR)的上丘进行了系统表征。我们检查了麻醉大鼠对上丘依赖的定向行为、局部场电位(LFP)和对视觉刺激的多单位反应,以及与Wistar Kyoto(WKY)和Wistar(WIS)相比SHR的形态学指标。我们发现,与对照品系相比,SHR对重复视觉刺激的反应次数更多,反应持续时间更长。此外,上丘视觉反应性浅层内的LFP和多单位活动表明,相对于对照品系,SHR的上丘反应过度,这不能通过视网膜-上丘通路功能改变来解释。最后,对上丘体积、神经元和胶质细胞密度以及胶质细胞与神经元比率的检查显示,相对于WKY,SHR的该比率降低,这可能解释了反应性增加的原因。总之,本研究证明了SHR上丘功能和结构的品系特异性变化,提供了趋同证据表明上丘在ADHD中可能功能失调。

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