Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing in Shank3-deficient rats.
Altered neural activity in the mesoaccumbens pathway underlies impaired social reward processing in Shank3-deficient rats.
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中伏隔通路神经活动的改变是 Shank3 缺陷大鼠社会奖励处理受损的基础。
DOI：
10.1101/2023.12.05.570134
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Harony-Nicolas,Hala
中科院分区：
文献类型：
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作者：
Barbier,Marie;ThirtamaraRajamani,Keerthi;Netser,Shai;Wagner,Shlomo;Harony-Nicolas,Hala
社会行为对人类的联系和归属感至关重要，经常受到自闭症谱系障碍（ASD）等疾病的影响。中伏隔核通路（VTA和NAc）在社会行为中起着关键作用，并与ASD有关。然而，自闭症相关突变对社会奖励加工的影响仍未得到充分探讨。本研究的重点是Shank3突变，与一种罕见的遗传疾病相关，并与ASD有关，使用Shank3缺陷大鼠模型，研究其在行为过程中对中伏隔核通路的影响。我们的研究结果表明，shank3缺陷大鼠表现出非典型的社会互动，难以根据奖励值调整行为，这与VTA多巴胺能和gaba能神经元的神经元活性改变以及NAc中多巴胺释放减少有关。此外，我们证明操纵VTA神经元活动可以使这种行为正常化，从而深入了解Shank3突变对社会奖励和行为的影响，并确定潜在的干预神经通路。
Social behaviors are crucial for human connection and belonging, often impacted in conditions like Autism Spectrum Disorder (ASD). The mesoaccumbens pathway (VTA and NAc) plays a pivotal role in social behavior and is implicated in ASD. However, the impact of ASD-related mutations on social reward processing remains insufficiently explored. This study focuses on the Shank3 mutation, associated with a rare genetic condition and linked to ASD, examining its influence on the mesoaccumbens pathway during behavior, using the Shank3-deficient rat model. Our findings indicate that Shank3-deficient rats exhibit atypical social interactions and have difficulty adjusting behavior based on reward values, associated with modified neuronal activity of VTA dopaminergic and GABAergic neurons and reduced dopamine release in the NAc. Moreover, we demonstrate that manipulating VTA neuronal activity can normalize this behavior, providing insights into the effects of Shank3 mutations on social reward and behavior, and identify a potential neural pathway for intervention.