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大鼠 A13 多巴胺能神经元参与抓握运动,但不参与奖励。

Involvement of A13 dopaminergic neurons in prehensile movements but not reward in the rat.

机构信息

Department of Neuroscience, Psychology & Behaviour, University of Leicester, University Road, Leicester LE1 9HN, UK.

Department of Neuroscience, Psychology & Behaviour, University of Leicester, University Road, Leicester LE1 9HN, UK.

出版信息

Curr Biol. 2023 Nov 20;33(22):4786-4797.e4. doi: 10.1016/j.cub.2023.09.044. Epub 2023 Oct 9.

Abstract

Tyrosine hydroxylase (TH)-containing neurons of the dopamine (DA) cell group A13 are well positioned to impact known DA-related functions as their descending projections innervate target regions that regulate vigilance, sensory integration, and motor execution. Despite this connectivity, little is known regarding the functionality of A13-DA circuits. Using TH-specific loss-of-function methodology and techniques to monitor population activity in transgenic rats in vivo, we investigated the contribution of A13-DA neurons in reward and movement-related actions. Our work demonstrates a role for A13-DA neurons in grasping and handling of objects but not reward. A13-DA neurons responded strongly when animals grab and manipulate food items, whereas their inactivation or degeneration prevented animals from successfully doing so-a deficit partially attributed to a reduction in grip strength. By contrast, there was no relation between A13-DA activity and food-seeking behavior when animals were tested on a reward-based task that did not include a reaching/grasping response. Motivation for food was unaffected, as goal-directed behavior for food items was in general intact following A13 neuronal inactivation/degeneration. An anatomical investigation confirmed that A13-DA neurons project to the superior colliculus (SC) and also demonstrated a novel A13-DA projection to the reticular formation (RF). These results establish a functional role for A13-DA neurons in prehensile actions that are uncoupled from the motivational factors that contribute to the initiation of forelimb movements and help position A13-DA circuits into the functional framework regarding centrally located DA populations and their ability to coordinate movement.

摘要

含酪氨酸羟化酶(TH)的多巴胺(DA)细胞群 A13 的神经元位于影响已知与 DA 相关功能的有利位置,因为其下行投射支配着调节警觉、感觉整合和运动执行的靶区。尽管存在这种连接性,但对于 A13-DA 回路的功能知之甚少。我们使用 TH 特异性功能丧失方法和技术,在转基因大鼠体内监测群体活动,研究了 A13-DA 神经元在奖励和运动相关动作中的作用。我们的工作表明 A13-DA 神经元在抓取和处理物体方面发挥作用,但与奖励无关。当动物抓取和操纵食物时,A13-DA 神经元会强烈反应,而其失活或退化会阻止动物成功抓取-这一缺陷部分归因于握力下降。相比之下,当动物在不包括抓取反应的基于奖励的任务中进行测试时,A13-DA 活动与觅食行为之间没有关系。食物的动机不受影响,因为在 A13 神经元失活/退化后,动物对食物的目标导向行为通常保持完整。一项解剖学研究证实 A13-DA 神经元投射到上丘(SC),并证明 A13-DA 神经元投射到网状结构(RF)的新联系。这些结果确立了 A13-DA 神经元在抓取动作中的功能作用,这些动作与有助于引发前肢运动的动机因素脱钩,并帮助将 A13-DA 回路置于中央位置的 DA 群体及其协调运动的功能框架中。

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