Lateral habenula neurocircuits mediate the maternal disruptive effect of maternal stress: A hypothesis

Up to 20% of women experience stress-related disorders during the postpartum period; however, little is known about the specific neural circuitry by which maternal stress exerts its negative impacts on mental health and maternal caregiving behavior. Theoretically, such a circuitry should serve as an interface between the stress response system and maternal neural network, transmitting stress signals to the neural circuitry that mediates maternal behavior. In this paper, I propose that the lateral habenula (LHb) serves this interface function. Evidence shows that the LHb plays a key role in encoding stress-induced effects and in the pathophysiology of major depression and stress-related anxiety, and thus may play a role in maternal behavior as part of the maternal brain network. I hypothesize that maternal stress acts upon the LHb and two of its major downstream targets, i.e., ventral tegmental area (VTA) and dorsal raphe nucleus (DRN), compromising the maternal care and contributing to postpartum mental disorders. This hypothesis makes three predictions: (1) maternal stress enhances LHb neuronal activity; (2) activation of DRN- and VTA-projecting neurons in the LHb mimics the detrimental effects of maternal stress on maternal behavior; and (3) suppression of DRN- and VTA-projecting neurons in the LHb attenuates the detrimental effects of maternal stress on maternal care in stressed mothers. Confirmation of this hypothesis is expected to enhance our understanding of the neurocircuit mechanisms mediating stress effects on maternal behavior.