Poster Presentation The International Congress of Neuroendocrinology 2014

Prolactin-sensitive GABAergic neurons contribute to the normal postpartum expression of maternal behaviour (#277)

Rosemary SE Brown 1 , Caroline M Larsen 1 , Sarah Cashen 1 , Amanda Wyatt 1 , Ilona C Kokay 1 , Penelope Knowles 1 , Paul R LeTissier 2 , Dave R Grattan 1
  1. University of Otago, Dunedin, New Zealand
  2. Institute of Child Health, London, United Kingdom

Prolactin is required for maternal behavior in rodents, acting within the medial preoptic nucleus (MPN). Using mice expressing tdTomato under control of the GABA-specific vesicular GABA transporter (vGat) promoter, we identified prolactin-induced pSTAT5 in many GABAergic neurons in the MPN. To test the hypothesis that these prolactin-sensitive GABAergic neurons mediate prolactin action to promote maternal behavior, we generated mice lacking Prlr in GABA neurons, and examined post-partum maternal behaviour. Mice with LoxP sites flanking the Prlr gene (PRLRflox) were crossed with mice expressing Cre-recombinase driven by vGAT (vGat-Cre), or the neuron-specific calcium-calmodulin-dependent Kinase-2α (CamK-Cre) promoter. Cre-mediated recombination could be detected through activation of a green fluorescent protein (GFP) construct within the transgene. Female mice homozygous for the PRLRflox and expressing Cre, and control mice that lacked Cre, were monitored over several estrous cycles, and then placed with a wildtype male and allowed to mate. While CamK-Cre mice had abnormal cycles characterized by prolonged diestrous, vGat-Cre cycles were normal.  Both groups were able to get pregnant and have an apparently normal pregnancy. The day of parturition was designated as postpartum day 1 (PPD1), and maternal behavior was tested on PPD2 using a pup-retrieval paradigm. Both lines of Cre-positive mice showed high levels of GFP in the medial preoptic nucleus (and other areas), indicating deletion of the prolactin receptor. Notably, vGAT-Cre mice had distinctive expression of GFP in the amygdala, and almost total loss of prolactin-induced pSTAT5 in this region.  vGat-Cre mice showed significantly impaired maternal behaviour, compared to control mice, suggesting that GABAergic neurons mediated some of prolactin action to stimulate maternal behaviour. CamK-Cre mice, however, showed markedly worse maternal behavior, suggesting that additional non-GABAergic neurons are also involved in prolactin action on maternal behavior.