Heterotrimeric G Proteins of the G q/11 Family Are Crucial for the Induction of Maternal Behavior in Mice

Abstract

Heterotrimeric G proteins of the Gq/11 family transduce signals from a variety of neurotransmitter receptors and have therefore been implicated in several functions of the central nervous system. To investigate the potential role of Gq/11 signaling in behavior, we generated mice which lack the α-subunits of the two main members of the Gq/11 family, Gαq and Gα11, selectively in the forebrain. We show here that forebrain Gαq/11-deficient females do not display any maternal behavior such as nest building, pup retrieving, crouching, or nursing. However, olfaction, motor behavior and mammary gland function are normal in forebrain Gαq/11-deficient females. We used c-fos immunohistochemistry to investigate pup-induced neuronal activation in different forebrain regions and found a significant reduction in the medial preoptic area, the bed nucleus of stria terminalis, and the lateral septum both in postpartum females and in virgin females after foster pup exposure. Pituitary function, especially prolactin release, was normal in forebrain Gαq/11-deficient females, and activation of oxytocin receptor-positive neurons in the hypothalamus did not differ between genotypes. Our findings show that Gq/11 signaling is indispensable to the neuronal circuit that connects the perception of pup-related stimuli to the initiation of maternal behavior and that this defect cannot be attributed to either reduced systemic prolactin levels or impaired activation of oxytocin receptor-positive neurons of the hypothalamus.