基因图谱确定了Homer1作为注意力发育修饰因子，这一成果由洛克菲勒大学Priya Rajasethupathy课题组经过不懈努力而取得。相关论文发表在2025年12月22日出版的《自然—神经科学》杂志上。

在这里，课题组采用无偏的正向遗传学方法来确定对注意力有很大影响的基因。该团队研究了200只遗传多样化的小鼠，通过遗传作图，在13号染色体上发现了一个小位点(95% CI 92.22-94.09 Mb)，这与注意前加工的变化显著相关。在这些位点中，该课题组研究人员发现了一个名为Homer1的基因，它编码一种突触蛋白，该基因在发育过程中的下调导致了成年后注意力的多项指标的改善。从机制上讲，Homer1水平的降低导致GABA受体的增加和前额叶皮层抑制性张力的增强，从而导致对噪音和注意力表现的神经信号的改善。他们确定了一个对注意力有重大影响的单一基因位点，并提出在发育敏感期形成的依赖于Homer1的抑制性音调，作为注意力表现的关键调节因子和潜在治疗靶点。

据了解，遗传因素和由此产生的神经回路生理驱动的注意力变化是知之甚少。

附：英文原文

Title: Genetic mapping identifies Homer1 as a developmental modifier of attention

Author: Gershon, Zachary, Bonito-Oliva, Alessandra, Kanke, Matt, Terceros, Andrea, Rankin, Genelle, Fak, John, Harada, Yujin, Iannone, Andrew F., Gebremedhin, Millennium, Fabella, Brian, De Marco Garca, Natalia V., Sethupathy, Praveen, Rajasethupathy, Priya

Issue&Volume: 2025-12-22

Abstract: The genetic factors and resulting neural circuit physiology driving variation in attention are poorly understood. Here we took an unbiased forward genetics approach to identify genes of large effect on attention. We studied 200 genetically diverse mice and, through genetic mapping, identified a small locus on chromosome 13 (95% CI 92.22–94.09Mb) that is significantly associated with variation in pre-attentive processing. Within the locus we identified a gene, Homer1, encoding a synaptic protein, whose downregulation during development led to improvements in multiple measures of attention in adulthood. Mechanistically, reduced Homer1 levels resulted in an upscaling of GABA receptors and enhanced inhibitory tone in the prefrontal cortex, leading to improved neural signal to noise and attentional performance. We thus identify a single genetic locus of large effect on attention and propose Homer1-dependent inhibitory tone, sculpted during a developmental sensitive period, as a key regulator and potential therapeutic target for attentional performance.

DOI: 10.1038/s41593-025-02155-2

Source: https://www.nature.com/articles/s41593-025-02155-2