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，同时抑制成年个体的负面情感状态——这类负面情感状态会在应对新生个体的应激困境时出现。目前，与负面情感相关的神经环路是否调控亲本行为仍未明确。本研究在接受终纹床核（bed nucleus of the stria terminalis, BNST）投射的外侧缰核（lateral habenula, LHb）神经元（简称BNSTLHb神经元）中，鉴定出与亲本抚育相关的细胞特征。我们发现，未交配雌鼠的外侧缰核神经元会在幼崽应激叫声（pup distress vocalization）出现后活动增强，且该神经元是幼崽叫声诱发厌恶行为的必要条件。在幼崽取回行为（pup retrieval）期间，外侧缰核活动会升高；而抑制外侧缰核的活动会恶化该行为。交叉细胞鉴定与转录组分析（transcriptional profiling）将BNSTLHb细胞与亲本抚育行为相关联，并揭示：未交配雌鼠的该类细胞基因表达谱与母鼠相似，但与非抚育型未交配雄鼠存在显著差异。最后，通过追踪并操控BNSTLHb细胞的活动，我们证实该细胞可特异性编码负面情感与幼崽取回行为。综上，一条负面情感神经环路可处理新生子代的应激信号，并通过调控雌性亲本的抚育行为来缓解这类应激信号带来的负面影响。