Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior

IF 6.7 2区医学 Q1 NEUROSCIENCES

Progress in Neurobiology Pub Date : 2024-10-20 DOI:10.1016/j.pneurobio.2024.102681

Myung Ji Kwak , Su Jeong Choi , Wen Ting Cai , Bo Ram Cho , Joonyeup Han , Jong Woo Park , Lars Björn Riecken , Helen Morrison , Se-Young Choi , Wha Young Kim , Jeong-Hoon Kim

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引用次数: 0

Abstract

Ezrin-Radixin-Moesin (ERM) proteins are actin-binding proteins that contribute to morphological changes in dendritic spines. Despite their significant role in regulating spine structure, the role of ERM proteins in the nucleus accumbnes (NAcc) is not well known, especially in in the context of risk-reward decision-making. Here, we measured the relationship between synaptic excitation and inhibition (E/I ratio) from medium spiny neurons in the NAcc core obtained in the rat after a rat gambling task (rGT). Then, after surgery of a phosphomimetic pseudo-active mutant form of radixin (Rdx-T564D) in the NAcc core, we examined its role in synaptic plasticity and the accompanying risk-choice behavior in rGT. We found that basal E/I ratio in the NAcc core was higher in risk-averse rats than risk-seeking rats. However, it was significantly reduced in risk-averse rats similar to that in risk-seeking rats in the presence of Rdx-T564D in the NAcc core. Furthermore, the head sizes of spines were shifted in risk-averse rats expressing Rdx-T564D in the NAcc core, similar to those observed in risk-seeking rats. The effects of Rdx-T564D in risk-averse rats were again manifested as behavioral changes, with reduced selection of optimal choices and increased selection of disadvantageous ones. In this study, we demonstrated that manipulation of radixin phosphorylation status in the NAcc core can alter glutamatergic synaptic transmission and spine structure at this site, as well as risk choice behaviors in the rGT. These novel findings illustrate that radixin in the NAcc core plays a significant role in determining risk preference during the rGT.

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操纵核团核心的 radixin 磷酸化可调节风险选择行为。

Ezrin-Radixin-Moesin（ERM）蛋白是一种肌动蛋白结合蛋白，有助于树突棘的形态变化。尽管ERM蛋白在调节棘突结构中起着重要作用，但它们在神经核accumbnes（NAcc）中的作用却不为人所知，尤其是在风险-回报决策中。在这里，我们测量了大鼠赌博任务（rGT）后获得的 NAcc 核心中中等棘神经元的突触兴奋和抑制（E/I 比值）之间的关系。然后，在对大鼠NAcc核心的Radixin（Rdx-T564D）磷拟假活性突变体进行手术后，我们研究了它在rGT中的突触可塑性和伴随的风险选择行为中的作用。我们发现，与寻求风险的大鼠相比，规避风险大鼠 NAcc 核心的基础 E/I 比率更高。然而，在NAcc核心存在Rdx-T564D的情况下，风险规避大鼠的E/I比值明显降低，与风险寻求大鼠相似。此外，在NAcc核心表达Rdx-T564D的风险厌恶型大鼠中，棘突的头部大小发生了偏移，这与在风险寻求型大鼠中观察到的情况相似。Rdx-T564D对风险规避大鼠的影响再次表现为行为变化，即对最优选择的选择减少，而对不利选择的选择增加。在这项研究中，我们证明了操纵 NAcc 核心的 radixin 磷酸化状态可以改变该部位的谷氨酸能突触传递和脊柱结构，以及 rGT 的风险选择行为。这些新发现说明，在rGT过程中，NAcc核心的radixin在决定风险偏好方面起着重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Progress in Neurobiology 医学-神经科学

CiteScore

12.80

自引率

1.50%

发文量

107

审稿时长

33 days

期刊介绍： Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.