PDF(Pubmed)
Abstract：
Social memory is the ability to discriminate between familiar and unknown conspecifics. It is an important component of social cognition and is therefore essential for the establishment of social relationships. Although the neural circuit mechanisms underlying social memory encoding have been well investigated, little focus has been placed on the regulatory mechanisms of social memory processing. The dopaminergic system, originating from the midbrain ventral tegmental area (VTA), is a key modulator of cognitive function. This study aimed to illustrate its role in modulating social memory and explore the possible molecular mechanisms. Here, we show that the activation of VTA dopamine (DA) neurons is required for the formation, but not the retrieval, of social memory. Inhibition of VTA DA neurons before social interaction, but not 24 h after social interaction, significantly impaired social discrimination the following day. In addition, we showed that the activation of VTA DA neurons was regulated by the serine/threonine protein kinase liver kinase B1 (Lkb1). Deletion of Lkb1 in VTA DA neurons reduced the frequency of burst firing of dopaminergic neurons. Furthermore, Lkb1 plays an important role in regulating social behaviors. Both genetic and virus-mediated deletions of Lkb1 in the VTA of adult mice impaired social memory and subsequently attenuated social familiarization. Altogether, our results provide direct evidence linking social memory formation to the activation of VTA DA neurons in mice and illustrate the crucial role of Lkb1 in regulating VTA DA neuron function.
摘要：
社会记忆是区分熟悉和未知物种的能力。它是社会认知的重要组成部分，因此对于建立社会关系至关重要。尽管社会记忆编码背后的神经回路机制已经得到了很好的研究，很少关注社会记忆处理的调节机制。多巴胺能系统,起源于中脑腹侧被盖区（VTA），是认知功能的关键调节剂。本研究旨在阐明其在调节社会记忆中的作用，并探讨其可能的分子机制。这里,我们表明，VTA多巴胺（DA）神经元的激活是形成所必需的，但不是检索，社会记忆。在社交互动之前抑制VTADA神经元，但不是在社交互动后24小时，第二天严重损害了社会歧视。此外,我们表明，VTADA神经元的激活受丝氨酸/苏氨酸蛋白激酶肝激酶B1（Lkb1）的调节。VTADA神经元中Lkb1的缺失降低了多巴胺能神经元爆发的频率。此外，Lkb1在调节社会行为中起着重要作用。成年小鼠VTA中Lkb1的遗传和病毒介导的缺失均损害了社会记忆，随后减弱了社会熟悉。总之,我们的研究结果提供了将社会记忆形成与小鼠VTADA神经元激活联系起来的直接证据，并说明了Lkb1在调节VTADA神经元功能中的关键作用。
