Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
J Neurosci. 2022 Jan 12;42(2):313-324. doi: 10.1523/JNEUROSCI.0741-21.2021. Epub 2021 Nov 29.
Neuronal activity in the prefrontal cortex (PFC) controls dominance hierarchies in groups of animals. Dopamine (DA) strongly modulates PFC activity mainly through D1 receptors (D1Rs) and D2 receptors (D2Rs). Still, it is unclear how these two subpopulations of DA receptor-expressing neurons in the PFC regulate social dominance hierarchy. Here, we demonstrate distinct roles for prefrontal D1R- and D2R-expressing neurons in establishing social hierarchy, with D1R neurons determining dominance and D2R neurons for subordinate. whole-cell recordings revealed that the dominant status of male mice correlates with rectifying AMPAR transmission and stronger excitatory synaptic strength onto D1R neurons in PFC pyramidal neurons. In contrast, the submissive status is associated with higher neuronal excitability in D2R neurons. Moreover, simultaneous manipulations of synaptic efficacy of D1R neurons in dominant male mice and neuronal excitability of D2R neurons of their male subordinates switch their dominant-subordinate relationship. These results reveal that prefrontal D1R and D2R neurons have distinct but synergistic functions in the dominance hierarchy, and DA-mediated regulation of synaptic strengths acts as a powerful behavioral determinant of intermale social rank. Dominance hierarchy exists widely among animals who confront social conflict. Studies have indicated that social status largely relies on the neuronal activity in the PFC, but how dopamine influences social hierarchy via subpopulation of prefrontal neurons is still elusive. Here, we explore the cell type-specific role of dopamine receptor-expressing prefrontal neurons in the dominance-subordinate relationship. We found that the synaptic strength of D1 receptor-expressing neurons determines the dominant status, whereas hyperactive D2-expressing neurons are associated with the subordinate status. These findings highlight how social conflicts recruit distinct cortical microcircuits to drive different behaviors and reveal how D1- and D2-receptor enriched neurocircuits in the PFC establish a social hierarchy.
前额皮质（PFC）中的神经元活动控制着动物群体中的优势等级。多巴胺（DA）通过 D1 受体（D1Rs）和 D2 受体（D2Rs）强烈调节 PFC 活动。然而，尚不清楚 PFC 中这两种表达 DA 受体的神经元亚群如何调节社会优势等级。在这里，我们证明了前额叶 D1R 和 D2R 表达神经元在建立社会等级制度中具有不同的作用，D1R 神经元决定优势，D2R 神经元决定从属。全细胞记录显示，雄性小鼠的支配地位与 PFC 锥体神经元中 AMPAR 传递的整流和 D1R 神经元上更强的兴奋性突触强度相关。相比之下，从属地位与 D2R 神经元中的更高神经元兴奋性相关。此外，对优势雄性小鼠的 D1R 神经元的突触效能和其雄性下属的 D2R 神经元的神经元兴奋性同时进行操作，可改变它们的主从关系。这些结果表明，前额叶 D1R 和 D2R 神经元在优势等级中具有不同但协同的功能，而 DA 介导的突触强度调节作为雄性间社会等级的强大行为决定因素。优势等级在面临社会冲突的动物中广泛存在。研究表明，社会地位在很大程度上依赖于 PFC 的神经元活动，但多巴胺如何通过前额叶神经元的亚群影响社会等级仍不清楚。在这里，我们探索了表达多巴胺受体的前额叶神经元在优势-从属关系中的细胞类型特异性作用。我们发现，D1 受体表达神经元的突触强度决定了支配地位，而过度活跃的 D2 表达神经元与从属地位相关。这些发现强调了社会冲突如何招募不同的皮质微电路来驱动不同的行为，并揭示了 PFC 中富含 D1 和 D2 受体的神经回路如何建立社会等级。
