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长期酒精暴露会在行为过程中差异性地改变纹状体细胞群的钙活性。

Chronic alcohol exposure differentially alters calcium activity of striatal cell populations during actions.

作者信息

Baltz Emily T, Renteria Rafael, Gremel Christina M

机构信息

The Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.

Department of Psychology, University of California San Diego, La Jolla, CA 92093, USA.

出版信息

Addict Neurosci. 2023 Dec;8. doi: 10.1016/j.addicn.2023.100128. Epub 2023 Sep 4.

Abstract

Alcohol Use Disorder (AUD) can induce long lasting alterations to executive function. This includes altered action control, which can manifest as dysfunctional goal-directed control. Cortical and striatal circuits mediate goal-directed control over behavior, and prior research has found chronic alcohol disrupts these circuits. In particular, prior in vivo and ex vivo work have identified alterations to function and activity of dorsal medial striatum (DMS), which is necessary for goal-directed control. However, unknown is whether these alterations manifest as altered activity of select DMS populations during behavior. Here we examine effects of prior chronic alcohol exposure on calcium activity modulation during action-related behaviors via fiber photometry of genetically-identified DMS populations including the direct and indirect output pathways, and fast-spiking interneurons. We find that prior chronic alcohol exposure leads to increased calcium modulation of the direct pathway during action related behavior. In contrast, prior chronic alcohol exposure led to decreased calcium activity modulation of the indirect pathway and the fast-spiking interneuron population around action-related events. Together, our findings suggest an imbalance in striatal activity during action control. This disruption may contribute to the altered goal-directed control previously reported.

摘要

酒精使用障碍(AUD)可导致执行功能的长期改变。这包括动作控制改变,可表现为功能失调的目标导向控制。皮质和纹状体回路介导对行为的目标导向控制,先前的研究发现慢性酒精会破坏这些回路。特别是,先前的体内和体外研究已经确定背内侧纹状体(DMS)的功能和活动发生改变,而DMS是目标导向控制所必需的。然而,尚不清楚这些改变是否表现为行为期间特定DMS群体的活动改变。在这里,我们通过对包括直接和间接输出途径以及快速放电中间神经元在内的基因鉴定的DMS群体进行纤维光度法,研究先前慢性酒精暴露对动作相关行为期间钙活动调节的影响。我们发现,先前慢性酒精暴露会导致动作相关行为期间直接途径的钙调节增加。相比之下,先前慢性酒精暴露会导致动作相关事件周围间接途径和快速放电中间神经元群体的钙活动调节降低。总之,我们的研究结果表明动作控制期间纹状体活动存在失衡。这种破坏可能导致先前报道的目标导向控制改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b49b/10569208/1ead3c44ef63/nihms-1932904-f0001.jpg

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