Next-generation sequencing of anterior cingulate cortex neurons in a social problem setting in rats

We studied the brain mechanisms of ‘social problem’ where a worker’s credit is exploited in a group setting. A stable ‘worker-parasite’ relationship developed when three individually operant-conditioned rats were placed together in a Skinner box equipped with response lever and food dispenser on opposite sides. Specifically, one rat, the ‘worker,’ engaged in lever-pressing while the other ‘parasitic’ rats profited by crowding the feeder in anticipation. c-Fos expression in the anterior cingulate cortex (ACC) was significantly higher in worker rats than in parasite rats. ACC inactivation suppressed the worker’s lever-press behavior under the social dilemma settings. Importantly, our RNA sequencing and the differential expression analysis showed that GABA- and potassium channel-related mRNA expressions decreased in the worker’s ACC. In contrast, network disinhibition induced-activity responsive genes such as Cyr61, Arc, and Klf are upregulated. These results suggest that downregulation and upregulation of network inhibitory and excitatory factors, respectively, in the ACC of the worker compared to parasite rats.本研究聚焦群体场景中劳动者劳动成果被侵占的「社交困境」问题，探究其背后的脑机制。当3只经过个体操作条件反射训练的大鼠被放置于配备对立侧操作杆与食物分发器的斯金纳箱（Skinner box）中时，会形成稳定的「劳动者-寄生者」关系。具体而言，其中1只作为「劳动者」的大鼠会执行压杆操作，其余2只「寄生」大鼠则通过提前聚集至食物进食区来获取奖励。相较于寄生者大鼠，劳动者大鼠的前扣带回皮层（anterior cingulate cortex，ACC）内c-Fos的表达水平显著升高。对前扣带回皮层进行失活处理，可抑制社交困境场景下劳动者的压杆行为。值得注意的是，本研究通过RNA测序（RNA sequencing）与差异表达分析发现，劳动者大鼠前扣带回皮层内，与γ-氨基丁酸（GABA）及钾离子通道相关的信使RNA（mRNA）表达水平出现下调。与之相反，网络去抑制诱导的活动响应基因如Cyr61、Arc及Klf的表达则出现上调。上述结果表明，与寄生者大鼠相比，劳动者大鼠前扣带回皮层内的网络抑制相关因子与兴奋性相关因子分别呈现下调与上调趋势。