--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 restricted CNS inactivation of the Oxtr KOs are able to lactate and their pups survive. This allows us to assess behaviors in mice with greatly reduced levels of Oxtr in specific regions. We previously 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 reduction in Avpr1a expression within the central amygdala that may account for the reduced behavior. This fiscal year we have begun studies in mice with reduction of the Oxtr in serotonin neurons. --We have continued our studies of the CA2 region of the hippocampus in several ways. We have submitted our neuroanatomical tracing findings in mice for publication. We have also been restoring Avpr1b expression in this region using lentiviruses and are currently analyzing our data. --Last 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 year, we applied this technique to control and Oxtr KO mice to look for differences in neuronal activity throughout their brains at rest and after social stresses. We are currently analyzing our data. --We finished our research on the microRNA 7 family and our analysis of the difficulty in discriminating between highly homologous members of the family is in press.

Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
2012
Total Cost
$1,990,068
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code
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
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
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
Young, W Scott; Song, June; Mezey, Éva (2016) Hybridization Histochemistry of Neural Transcripts. Curr Protoc Neurosci 75:1.3.1-1.3.27
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
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
Young, W Scott (2013) Shedding heat on oxytocin. Endocrinology 154:3961-2
Colaianni, Graziana; Sun, Li; Di Benedetto, Adriana et al. (2012) Bone marrow oxytocin mediates the anabolic action of estrogen on the skeleton. J Biol Chem 287:29159-67
Malkesman, Oz; Austin, Daniel R; Tragon, Tyson et al. (2012) Acute D-serine treatment produces antidepressant-like effects in rodents. Int J Neuropsychopharmacol 15:1135-48
Pobbe, Roger L H; Pearson, Brandon L; Defensor, Erwin B et al. (2012) Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors. Horm Behav 61:436-44

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