The Lateral Habenula Is Necessary for Maternal Behavior in the Naturally Parturient Primiparous Mouse Dam

Mammalian parenting is an unusually demanding commitment. How has the reward system been co-opted 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 primiparous mouse dams. We show that kainic acid lesions of the LHb induced a severe maternal neglect phenotype in dams toward their biological pups. Next, we demonstrate that chronic chemogenetic inactivation of the LHb using inhibitory DREADDs impaired acquisition and performance of various maternal behaviors, such as pup retrieval and nesting. We present a random intercept model suggesting LHb inactivation prevents the acquisition of pup retrieval, a novel maternal behavior in primiparous mouse dams, 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 intercept model, which suggests 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.