A neural substrate for negative affect dictates female parental behavior

Parental behaviors secure the well-being of newborns and concomitantly limit negative affective states in adults, which emerge when coping with neonatal distress becomes challenging. Whether negative-affect-related neuronal circuits orchestrate parental actions is unknown. Here, we identify parental signatures in lateral habenula neurons receiving bed nucleus of stria terminalis innervation (^BNSTLHb). We find that LHb neurons of virgin female mice increase their activity following pup distress vocalization and are necessary for pup-call-driven aversive behaviors. LHb activity rises during pup retrieval, a behavior worsened by LHb inactivation. Intersectional cell identification and transcriptional profiling associate ^BNSTLHb cells to parenting and outline a gene expression in female virgins similar to that in mothers but different from that in non-parental virgin male mice. Finally, tracking and manipulating ^BNSTLHb cell activity demonstrates their specificity for encoding negative affect and pup retrieval. Thus, a negative affect neural circuit processes newborn distress signals and may limit them by guiding female parenting.亲本行为可保障新生子代的福祉，同时缓解成年个体在应对幼崽痛苦应激时产生的负面情绪状态。目前尚不明确，与负面情绪相关的神经环路是否会调控亲本抚育行为。本研究在接受终纹床核（bed nucleus of stria terminalis, BNST）传入投射的外侧缰核（lateral habenula, LHb）神经元中，鉴定出了与亲本抚育相关的特征性神经活性。我们发现，未生育雌性小鼠的外侧缰核神经元会在幼崽发出痛苦叫声后激活，且该神经元群体是介导幼崽叫声引发的厌恶行为所必需的。幼崽取回行为过程中，外侧缰核神经元活性升高；抑制外侧缰核活性则会损害该育幼行为。交叉细胞鉴定与转录组谱分析表明，接受终纹床核投射的外侧缰核神经元与亲本抚育行为密切相关，且未生育雌性小鼠的该类神经元的基因表达谱与母鼠相似，但与未经历育幼的未生育雄性小鼠存在显著差异。最后，通过追踪与操控接受终纹床核投射的外侧缰核神经元活性，我们证实了该类神经元可特异性编码负面情绪与幼崽取回行为。综上，一条负面情绪相关神经环路可感知新生子代的痛苦信号，并通过调控雌性亲本抚育行为来缓解此类负面应激状态。