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 (LHb). 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 LHb 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 LHb 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.