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多巴胺转运体基因敲除(DAT-KO)大鼠中多巴胺能亢进的电生理和行为学标志物

Electrophysiological and Behavioral Markers of Hyperdopaminergia in DAT-KO Rats.

作者信息

Fesenko Zoia, Ptukha Maria, da Silva Marcelo M, de Carvalho Raquel S Marques, Tsytsarev Vassiliy, Gainetdinov Raul R, Faber Jean, Volnova Anna B

机构信息

Institute of Translational Biomedicine, Saint Petersburg State University, Saint Petersburg 199034, Russia.

Centre for Youth Mental Health, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria 3010, Australia.

出版信息

Biomedicines. 2024 Sep 17;12(9):2114. doi: 10.3390/biomedicines12092114.

Abstract

Dopamine dysfunction (DA) is a hallmark of many neurological disorders. In this case, the mechanism of changes in dopamine transmission on behavior remains unclear. This study is a look into the intricate link between disrupted DA signaling, neuronal activity patterns, and behavioral abnormalities in a hyperdopaminergic animal model. To study the relationship between altered DA levels, neuronal activity, and behavioral deficits, local field potentials (LFPs) were recorded during four different behaviors in dopamine transporter knockout rats (DAT-KO). At the same time, local field potentials were recorded in the striatum and prefrontal cortex. Correlates of LFP and accompanying behavioral patterns in genetically modified (DAT-KO) and control animals were studied. DAT-KO rats exhibited desynchronization between LFPs of the striatum and prefrontal cortex, particularly during exploratory behavior. A suppressive effect of high dopamine levels on the striatum was also observed. Wild-type rats showed greater variability in LFP patterns across certain behaviors, while DAT-KO rats showed more uniform patterns. The decisive role of the synchrony of STR and PFC neurons in the organization of motor acts has been revealed. The greater variability of control animals in certain forms of behavior probably suggests greater adaptability. More uniform patterns in DAT-KO rats, indicating a loss of striatal flexibility when adapting to specific motor tasks. It is likely that hyperdopaminergy in the DAT-KO rat reduces the efficiency of information processing due to less synchronized activity during active behavior.

摘要

多巴胺功能障碍(DA)是许多神经疾病的一个标志。在这种情况下,多巴胺传递变化对行为的影响机制仍不清楚。本研究旨在探究多巴胺能亢进动物模型中多巴胺信号传导中断、神经元活动模式和行为异常之间的复杂联系。为了研究多巴胺水平改变、神经元活动和行为缺陷之间的关系,在多巴胺转运体基因敲除大鼠(DAT-KO)的四种不同行为过程中记录了局部场电位(LFP)。同时,在纹状体和前额叶皮层记录局部场电位。研究了转基因(DAT-KO)动物和对照动物中LFP与伴随行为模式的相关性。DAT-KO大鼠的纹状体和前额叶皮层的LFP之间表现出不同步,特别是在探索行为期间。还观察到高多巴胺水平对纹状体的抑制作用。野生型大鼠在某些行为中的LFP模式表现出更大的变异性,而DAT-KO大鼠的模式则更为一致。已揭示出纹状体和前额叶皮层神经元同步性在运动行为组织中的决定性作用。对照动物在某些行为形式中更大的变异性可能表明其具有更强的适应性。DAT-KO大鼠更为一致的模式表明,在适应特定运动任务时纹状体灵活性丧失。DAT-KO大鼠中的多巴胺能亢进可能由于主动行为期间活动同步性降低而降低了信息处理效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77c6/11428849/c0ecf0b2ace0/biomedicines-12-02114-g001.jpg

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