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Senior Investigator

Scott Young, M.D., Ph.D.

Section on Neural Gene Expression

Section on Neural Gene Expression
Building 49 Room 5A56
9000 Rockville Pike,
Bethesda MD 20892-4483
Office: (301) 496-8767

Fax: (301) 402-6473
wsy@mail.nih.gov

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 using and creating knock-out and transgenic mice, optogenetics, electrophysiology, calcium-imaging and other techniques 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. 

We made mice lacking Oxt, as well as the first conditional knockout of the oxytocin receptor (Oxtr). Inactivation of the Oxtr in forebrain excitatory neurons decreases fear conditioning. We found that 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 hippocampus, 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 . 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. Most recently, we demonstrated  that optogenetic stimulation of vasopressin fibers within the mouse CA2 strongly enhances social, but not object memory. This vasopressin release from fibers arising in the paraventricular nucleus, lengthens the social memory by at least 80 fold and is inhibited by a locally infused Avpr1b antagonist. In addition, the enhancement is produced by stimulation during the acquisition phase of the memory and not during the recall phase.

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  • Adi Cymerblit-Sabba, Ph.D.
    Predoctoral Fellow

  • Emily Shepard, B.S.
    Biologist
    (301) 496-0716

  • Adam Smith, Ph.D.
    Postdoctoral Fellow

  • June Song, B.S.
    Biologist

  • Sarah Williams, Ph.D.
    Postdoctoral Fellow
    (301) 594-2768

  • 1) Smith AS, Williams Avram SK, Cymerblit-Sabba A, Song J, Young WS. (2016)
  • Targeted activation of the hippocampal CA2 area strongly enhances social memory.
  • Mol Psychiatry, Epub Jan 5
  • 2) Pagani JH, Williams Avram SK, Cui Z, Song J, Mezey É, Senerth JM, Baumann MH, Young WS. (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
  • 3) Pagani JH, Zhao M, Cui Z, Williams Avram SK, Caruana DA, Dudek SM, Young WS (2014)
  • Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2
  • Mol Psychiatry
  • 4) Cui Z, Gerfen CR, Young WS (2013)
  • Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus
  • J Comp Neurol, 521, 1844-66
  • 5) Mok SI, Munasinghe JP, Young WS (2011)
  • Infusion-based manganese-enhanced MRI: a new imaging technique to visualize the mouse brain
  • Brain Struct Funct
  • 6) Pagani JH, Lee HJ, Young WS (2011)
  • Postweaning, forebrain-specific perturbation of the oxytocin system impairs fear conditioning
  • Genes Brain Behav, 10, 710-19
  • 7) DeVito LM, Konigsberg R, Lykken C, Sauvage M, Young WS 3rd, Eichenbaum H. (2009)
  • Vasopressin 1b receptor knock-out impairs memory for temporal order
  • J Neurosci, 29, 2676-83
  • 8) Macbeth AH, Lee HJ, Edds J, Young WS 3rd (2009)
  • Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition
  • Genes Brain Behav, 8, 558-67
  • 9) Lee HJ, Macbeth AH, Pagani JH, Young WS 3rd. (2009)
  • Oxytocin: the great facilitator of life
  • Prog Neurobiol, 88, 127-51
  • 10) Caldwell HK, Stephens SL, Young WS 3rd (2009)
  • Oxytocin as a natural antipsychotic: a study using oxytocin knockout mice
  • Mol Psychiatry, 14, 190-96
  • 11) Lee HJ, Caldwell HK, Macbeth AH, Tolu SG, Young WS 3rd (2008)
  • A conditional knockout mouse line of the oxytocin receptor
  • Endocrinology, 149, 3256-63
  • 12) Caldwell HK, Lee HJ, Macbeth AH, Young WS 3rd. (2007)
  • Vasopressin: behavioral roles of an original neuropeptide
  • Prog Neurobiol, 84, 1-24
  • 13) Wersinger SR, Caldwell HK, Christiansen M, Young WS 3rd (2007)
  • Disruption of the vasopressin 1b receptor gene impairs the attack component of aggressive behavior in mice
  • Genes Brain Behav, 6, 653-60
  • 14) Crawley JN, Chen T, Puri A, Sullivan TL, Hill JM, Young NB, Nadler JJ, Moy SS, Young LJ, Caldwell J, Young WS (2007)
  • Social approach behaviors in oxytocin knockout mice: Comparison of two independent lines tested in different laboratory environments
  • Neuropeptides, 41, 145-163
  • 15) Young WS, Li J, Wersinger SR, Palkovits M (2006)
  • The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy
  • Neuroscience, 143, 1031-9
  • 16) Lee HJ, Palkovits M, Young WS 3rd (2006)
  • miR-7b, a microRNA up-regulated in the hypothalamus after chronic hyperosmolar stimulation, inhibits Fos translation
  • Proc Natl Acad Sci U S A., 103, 15669-74
  • 17) Wersinger SR, Kelliher KR, Zufall F, Lolait SJ, O'Carroll AM, Young WS 3rd (2004)
  • Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task
  • Horm. Behav., 46, 638-45
  • 18) Wersinger, SR, Ginns, EI, O'Carroll, AM, Lolait, SJ, and Young, WS 3rd (2002)
  • Vasopressin V1b receptor knockout reduces aggressive behavior in male mice
  • Mol. Psychiat., 7, 975-84
  • 19) Gainer H, Young WS 3rd (2001)
  • Transgenic Models for Studies of Oxytocin and Vasopressin
  • in Castro, E.M. (ed.) Transgenic Models in Endocrinology,, Kluwer Academic Press, Boston, 25-46
  • 20) Young WS 3rd, Iacangelo A, Luo XZ J, King C, Duncan K, Ginns, EI (1999)
  • Transgenic expression of green fluorescent protein in mouse oxytocin neurons
  • J. Neuroendocrinol, 11, 935-940
  • 21) Young WS 3rd, Shepard E, Amico J, Hennighausen L, Wagner KU, LaMarca ME, McKinney C, Ginns, EI (1996)
  • Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition
  • J. Neuroendocrinol., 8, 847-853
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