--We have continued this fiscal year to study our gene knockouts (KO) of the mouse oxytocin (Oxt) and vasopressin (Avp) 1a and 1b receptors (Oxtr, Avpr1a and Avpr1b, respectively) to investigate their specific roles in mediating behavior. We are also continuing to analyze whether we were successful in creating a conditional KO of the Avpr1b gene that would allow more precise spatial and temporal regulation of its expression. Avp and Oxt are neurohormones that are best known for their peripheral actions in regulating salt and water balance, blood pressure, lactation and parturition. However, numerous pharmacological studies have implicated these hormones in various behaviors as well, including aggressive, affiliative, social recognition, fear conditioning and maternal. --We recently started studying a conditional KO of the Oxt receptor (Oxtr). This line has the coding region flanked by special DNA sequences to allow us to temporally and spatially regulate the expression of the Oxtr. Unlike Oxt and total Oxtr KOs, mice with relatively forebrain-specific inactivation of the Oxtr KOs (that begins after weaning) are able to lactate and their pups survive. This allows us to assess behaviors in mice with greatly reduced levels of Oxtr in their forebrains. We assessed fear conditioning in these mice and showed that they have reduced fear conditioning (as opposed to normal fear conditioning in total Avpr1a or Oxtr KOs). We determined that these mice also have a reductionin Avpr1a expression within the central amygdala that may account for the reduced behavior. --This fiscal year, we showed that it is possible to measure neuronal activity in freely behaving mice. We did this through the use of a novel approach to magnetic resonance imaging (MRI). We implanted mini Alzet pumps into the mice to release manganese chloride peripherally. The manganese is taken up by neurons in proportion to their activity. This manganese-enhanced MRI (MEMRI) technique will be applied next to control and KO mice to look for differences in neuronal activity throughout their brains. --We created heterozygote KOs of a small, non-coding RNA, miR-7b, that we discovered regulates levels of an important gene regulator, c-Fos. Preliminary indications are that the homozygous KOs are not viable. We will attempt to determine why that is the case. Also, we will attempt to use virally-mediated knock down of the microRNA to pursue its role in regulating gene expression.

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Young, W Scott; Song, June; Mezey, Éva (2018) Hybridization Histochemistry of Neural Transcripts. Curr Protoc Neurosci 82:1.3.1-1.3.27
Mayer, Balázs; Németh, Krisztián; Krepuska, Miklós et al. (2017) Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia. Sci Transl Med 9:
Oettl, Lars-Lennart; Ravi, Namasivayam; Schneider, Miriam et al. (2016) Oxytocin Enhances Social Recognition by Modulating Cortical Control of Early Olfactory Processing. Neuron 90:609-21
Young, W Scott; Song, June; Mezey, Éva (2016) Hybridization Histochemistry of Neural Transcripts. Curr Protoc Neurosci 75:1.3.1-1.3.27
Patial, Sonika; Stumpo, Deborah J; Young 3rd, W Scott et al. (2016) Effects of Combined Tristetraprolin/Tumor Necrosis Factor Receptor Deficiency on the Splenic Transcriptome. Mol Cell Biol 36:1395-411
Smith, A S; Williams Avram, S K; Cymerblit-Sabba, A et al. (2016) Targeted activation of the hippocampal CA2 area strongly enhances social memory. Mol Psychiatry 21:1137-44
Pagani, J H; Zhao, M; Cui, Z et al. (2015) Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. Mol Psychiatry 20:490-9
Pagani, J H; Williams Avram, S K; Cui, Z et al. (2015) Raphe serotonin neuron-specific oxytocin receptor knockout reduces aggression without affecting anxiety-like behavior in male mice only. Genes Brain Behav 14:167-76
Choi, Ji-Woong; Kang, Sung-Min; Lee, Youngkyun et al. (2013) MicroRNA profiling in the mouse hypothalamus reveals oxytocin-regulating microRNA. J Neurochem 126:331-7
Young, W Scott (2013) Shedding heat on oxytocin. Endocrinology 154:3961-2

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