Dodis Grace, Choi Sanghoon, Flanigan Meghan
Department of Neuroscience, Medical University of South Carolina, 70 President Street, Rm 210, Charleston, SC, 29425, USA.
Psychopharmacology (Berl). 2025 Oct 20. doi: 10.1007/s00213-025-06911-x.
The lateral habenula (LHb) is classically associated with processing aversive stimuli and suppressing reward-driven behavior. Recent work, however, redefines the LHb as a node that not only mediates antisocial and avoidant behaviors but also regulates prosocial engagement and social motivation. As a convergence point for forebrain inputs and a driver of midbrain output, we review how the LHb contributes to behavioral outcomes in aggression, social avoidance, caregiving, and social memory. Cell-type-specific investigations reveal that glutamatergic (vGlut2⁺) and GABAergic (GAD2⁺) LHb neurons play dissociable roles in shaping aggression, social avoidance, and social cognition, while serotonin 2c receptor (5-HT) expressing neurons may represent a molecularly distinct sub-population differentially influencing social behaviors in males and females. These findings suggest that LHb circuits encode the valence and salience of social cues and flexibly adjust behavioral output in contextually appropriate and adaptive ways. Disruption of these pathways from stress, early adversity, or genetic susceptibility may underlie rigid or maladaptive social phenotypes. By mapping the input-output architecture and functional diversity of LHb subcircuits, future studies incorporating specific cell types and circuits will further unravel the complicated nature of how social decisions are dynamically regulated in the LHb and how dysregulated LHb activity may contribute to social symptoms of psychiatric disease.
外侧缰核(LHb)传统上与处理厌恶刺激和抑制奖励驱动行为有关。然而,最近的研究将LHb重新定义为一个节点,它不仅介导反社会和回避行为,还调节亲社会参与和社会动机。作为前脑输入的汇聚点和中脑输出的驱动者,我们综述了LHb如何在攻击、社会回避、照料和社会记忆等行为结果中发挥作用。细胞类型特异性研究表明,谷氨酸能(vGlut2⁺)和γ-氨基丁酸能(GAD2⁺)的LHb神经元在塑造攻击、社会回避和社会认知方面发挥着不同的作用,而表达5-羟色胺2c受体(5-HT)的神经元可能代表一个分子上不同的亚群,对雄性和雌性的社会行为有不同的影响。这些发现表明,LHb回路编码社会线索的效价和显著性,并以上下文适当和适应性的方式灵活调整行为输出。来自压力、早期逆境或遗传易感性对这些通路的破坏可能是僵化或适应不良社会表型的基础。通过绘制LHb子回路的输入-输出结构和功能多样性,未来结合特定细胞类型和回路的研究将进一步揭示LHb中社会决策如何动态调节的复杂本质,以及LHb活动失调如何导致精神疾病的社会症状。