Heterotrimeric G proteins of the Gq/11 family are crucial for the induction of maternal behavior in mice.
Heterotrimeric G proteins of the G(q/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 G(q/11) signaling in behavior, we generated mice which lack the alpha-subunits of the two main members of the G(q/11) family, Galpha(q) and Galpha(11), selectively in the forebrain. We show here that forebrain Galpha(q/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 Galpha(q/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 Galpha(q/11)-deficient females, and activation of oxytocin receptor-positive neurons in the hypothalamus did not differ between genotypes. Our findings show that G(q/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.
Wettschureck
Nina
N
Institute of Pharmacology, University of Heidelberg, Germany. Nina.Wettschureck@urz.uni-heidelberg.de
Moers
Alexandra
A
Hamalainen
Tuula
T
Lemberger
Thomas
T
Schütz
Günther
G
Offermanns
Stefan
S
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011247:Pregnancy; D011301:Preoptic Area / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology; D018045:Receptors, Oxytocin / Q000502:physiology; D015398:Signal Transduction
D018045:Receptors, Oxytocin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11