美国洛克菲勒大学Priyamvada Rajasethupathy、康奈尔大学Praveen Sethupathy等研究人员合作发现，丘脑的孤儿受体驱动短期记忆的可变性。相关论文于2020年9月29日在线发表在《细胞》杂志上。

研究人员表示，工作记忆是短期记忆的一种形式，涉及维护和更新与任务相关的信息，从而达到目标导向的追求。经典模型将前额叶皮层（PFC）中的持续活动定位为主要的神经相关因素，但新观点表明可能存在其他机制。

研究人员筛选了约200只在工作记忆任务中具有遗传多样性的小鼠，并确定了5号染色体上的遗传位点，该基因位点占表型变异的很大一部分（17％）。在基因座内，研究人员鉴定了一个编码孤儿G蛋白偶联受体Gpr12的基因，该基因足以驱动工作记忆中的实质性和双向变化。分子、细胞和影像学研究表明，Gpr12使丘脑-PFC高度同步，从而支持记忆维持和选择准确性。

这些发现确定了孤儿受体是短期记忆的有效修饰因子，并以新兴的丘脑中心框架补充了基于PFC的经典模型，从而对工作记忆进行了机制性理解。

附：英文原文

Title: A Thalamic Orphan Receptor Drives Variability in Short-Term Memory

Author: Kuangfu Hsiao, Chelsea Noble, Wendy Pitman, Nakul Yadav, Suraj Kumar, Gregory R. Keele, Andrea Terceros, Matt Kanke, Tara Conniff, Christopher Cheleuitte-Nieves, Ravi Tolwani, Praveen Sethupathy, Priyamvada Rajasethupathy

Issue&Volume: 2020-09-28

Abstract: Working memory is a form of short-term memory that involves maintaining and updatingtask-relevant information toward goal-directed pursuits. Classical models posit persistentactivity in prefrontal cortex (PFC) as a primary neural correlate, but emerging viewssuggest additional mechanisms may exist. We screened ～200 genetically diverse miceon a working memory task and identified a genetic locus on chromosome 5 that contributesto a substantial proportion (17%) of the phenotypic variance. Within the locus, weidentified a gene encoding an orphan G-protein-coupled receptor, Gpr12, which is sufficient to drive substantial and bidirectional changes in working memory.Molecular, cellular, and imaging studies revealed that Gpr12 enables high thalamus-PFC synchrony to support memory maintenance and choice accuracy.These findings identify an orphan receptor as a potent modifier of short-term memoryand supplement classical PFC-based models with an emerging thalamus-centric frameworkfor the mechanistic understanding of working memory.

DOI: 10.1016/j.cell.2020.09.011

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31152-1