Principal Investigator: Scott Young
Section on Neural Gene Expression (SNGE)
Laboratory of Cellular and Molecular Regulation
Dr. Young received his B.A., M.D. and Ph.D from The Johns Hopkins University. The latter degree, obtained under the guidance of Michael Kuhar, described the development of in vitro receptor autoradiography and the first applications of the technique to the localization of neurotranmsitter receptors in human and other animal brains. Dr. Young then completed an internship in internal medicine at the University of Maryland and a residency in neurology at the University of Virginia. He joined the NIMH in 1984 where he has studied the paraventricular and supraoptic nuclei in the hypothalamus. Dr. Young's laboratory is currently creating and using knock-out and transgenic mice to study the roles of vasopressin and oxytocin in the brain.
The Section on Neural Gene Expression investigates the roles and regulation of expression of vasopressin (Avp) and oxytocin (Oxt) in the central nervous system. They are peptide hormones that are composed of 9 amino acids and that participate in the regulation of fluid balance, parturition and lactation. In addition, they have important roles in various behaviors, including social and maternal ones, through their actions mediated by at least 3 receptors in the brain.
Our group uses a variety of techniques, including anatomical (hybridization histochemistry and receptor autoradiography), molecular biological, transgenic animals, optogenetics, and electrophysiology to explore behavior in the mouse. For example, we have generated mice lacking functional Oxt , as well as mice that express green fluorescent protein in Oxt neurons, in our attempts to determine the essential and non-essential roles of this hormone. We also created the first conditional knockout of the oxytocin receptor (Oxtr) and are using them to further our knowledge of Oxt's role in behavior. For example, inactivation of the Oxtr in forebrain excitatory neurons decreases fear conditioning . We also showed that the Oxtr is necessary for intra-strain, but not inter-strain, social recognition .
Our latest work examines the role of the vasopressin 1b receptor (Avpr1b) in the brain. It is found predominantly in the CA2 region of the hiipocampus, an area that receives innervation from the AVP-producing paraventricular nucleus of the hypothalamus. We made Avpr1b knockout mice to inactivate the receptor and observed that these mice have a marked reduction in social, but not predatory or defensive, aggression in males and females . They also have modest declines in social recognition in males and females . Recently, we showed that viral replacement of Avpr1b in the CA2 area of the mouse hippocampus in these knockout mice restores aggression. Furthermore, the Avpr1b (and Oxtr) enables significant potentiation of excitatory synaptic responses in CA2, but not in CA1 or in slices from Avpr1b (and Oxtr, respectively) knockout mice.
Our various studies with transgenic, including knockout mice, are listed here.
Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2 . Pagani JH, Zhao M, Cui Z, Williams Avram SK, Caruana DA, Dudek SM, Young WS. Mol Psychiatry. 2014 May 27. doi: 10.1038/mp.2014.47 PMID: 24863146.
Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus . Cui Z, Gerfen CR, Young WS 3rd. J Comp Neurol. 2013 Jun 1;521(8):1844-66. doi: 10.1002/cne.23263 PMID: 23172108.
Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain . Mok SI, Munasinghe JP, Young WS. Brain Struct Funct. 2012 Jan;217(1):107-14. doi: 10.1007/s00429-011-0324-y. Epub 2011 May 20. PMID: 21597966.
Postweaning, forebrain-specific perturbation of the oxytocin system impairs fear conditioning . Pagani JH, Lee HJ, Young WS 3rd. Genes Brain Behav. 2011 Oct;10(7):710-9. doi: 10.1111/j.1601-183X.2011.00709.x. Epub 2011 Jul 1. PMID: 21668734.
Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition . Macbeth AH, Lee HJ, Edds J, Young WS 3rd. Genes Brain Behav. 2009 Jul;8(5):558-67. doi: 10.1111/j.1601-183X.2009.00506.x. Epub 2009 May 21. PMID: 19531157.
Vasopressin 1b receptor knock-out impairs memory for temporal order . DeVito LM, Konigsberg R, Lykken C, Sauvage M, Young WS 3rd, Eichenbaum H. J Neurosci. 2009 Mar 4;29(9):2676-83. doi: 10.1523/JNEUROSCI.5488-08.2009. PMID: 19261862.
Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice . Caldwell HK, Stephens SL, Young WS 3rd. Mol Psychiatry. 2009 Feb;14(2):190-6. doi: 10.1038/sj.mp.4002150. Epub 2008 Jan 29. PMID: 18227836.
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