The lateral habenula is required for maternal behavior in the mouse dam.

UNLABELLED: Mammalian parenting is an unusually demanding commitment. How did evolution co-opt the reward system to ensure parental care? Previous work has implicated the lateral habenula (LHb), an epithalamic nucleus, as a potential intersection of parenting behavior and reward. Here, we examine the role of the LHb in the maternal behavior of naturally parturient mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams towards their biological pups. Next, we demonstrate that through chronic chemogenetic inactivation of the LHb using DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercepts model suggesting LHb-inactivation prevents the acquisition of the novel pup retrieval maternal behavior and decreases nest building performance, an already-established behavior, in primiparous mouse dams. Lastly, we examine the spatial histology of kainic-acid treated dams with a random intercepts model, which suggests that the role of LHb in maternal behavior may be preferentially localized at the posterior aspect of this structure. Together, these findings serve to establish the LHb as required for maternal behavior in the mouse dam, thereby complementing previous findings implicating the LHb in parental behavior using pup-sensitized virgin female mice.

SIGNIFICANCE STATEMENT: Work conducted using rats in the 1990s suggested an important role for the LHb in maternal behavior, but this area of research has since lain dormant. In the interim, the LHb has been garnering attention as a hub for punishment signaling. Recently, interest in the LHb's role in maternal behavior was renewed, with an important paper examining LHb function during pup-directed behaviors in pup-sensitized virgin female mice. But it is unknown how closely pup-directed behaviors in sensitized virgin females may mimic maternal behavior in natural mouse mothers. This work demonstrates the importance of the LHb in the regulation of natural maternal behavior in the mouse.