Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions

Vaishnav Krishnan, Ming Hu Han, Danielle L. Graham, Olivier Berton, William Renthal, Scott J. Russo, Quincey LaPlant, Ami Graham, Michael Lutter, Diane C. Lagace, Subroto Ghose, Robin Reister, Paul Tannous, Thomas Green, Rachael L. Neve, Sumana Chakravarty, Arvind Kumar, Amelia J. Eisch, David W. Self, Francis S. Lee & 4 others Carol A. Tamminga, Donald C. Cooper, Howard K. Gershenfeld, Eric J. Nestler

Research output: Contribution to journalArticle

1024 Citations (Scopus)

Abstract

While stressful life events are an important cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The molecular mechanisms underlying such resilience are poorly understood. Here, we demonstrate that an inbred population of mice subjected to social defeat can be separated into susceptible and unsusceptible subpopulations that differ along several behavioral and physiological domains. By a combination of molecular and electrophysiological techniques, we identify signature adaptations within the mesolimbic dopamine circuit that are uniquely associated with vulnerability or insusceptibility. We show that molecular recapitulations of three prototypical adaptations associated with the unsusceptible phenotype are each sufficient to promote resistant behavior. Our results validate a multidisciplinary approach to examine the neurobiological mechanisms of variations in stress resistance, and illustrate the importance of plasticity within the brain's reward circuits in actively maintaining an emotional homeostasis.

Original languageEnglish (US)
Pages (from-to)391-404
Number of pages14
JournalCell
Volume131
Issue number2
DOIs
StatePublished - Oct 19 2007
Externally publishedYes

Fingerprint

Psychopathology
Reward
Dopamine
Brain
Homeostasis
Psychology
Phenotype
Networks (circuits)
Population
Plasticity

Keywords

  • MOLNEURO
  • SYSNEURO

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Krishnan, V., Han, M. H., Graham, D. L., Berton, O., Renthal, W., Russo, S. J., ... Nestler, E. J. (2007). Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions. Cell, 131(2), 391-404. https://doi.org/10.1016/j.cell.2007.09.018

Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions. / Krishnan, Vaishnav; Han, Ming Hu; Graham, Danielle L.; Berton, Olivier; Renthal, William; Russo, Scott J.; LaPlant, Quincey; Graham, Ami; Lutter, Michael; Lagace, Diane C.; Ghose, Subroto; Reister, Robin; Tannous, Paul; Green, Thomas; Neve, Rachael L.; Chakravarty, Sumana; Kumar, Arvind; Eisch, Amelia J.; Self, David W.; Lee, Francis S.; Tamminga, Carol A.; Cooper, Donald C.; Gershenfeld, Howard K.; Nestler, Eric J.

In: Cell, Vol. 131, No. 2, 19.10.2007, p. 391-404.

Research output: Contribution to journalArticle

Krishnan, V, Han, MH, Graham, DL, Berton, O, Renthal, W, Russo, SJ, LaPlant, Q, Graham, A, Lutter, M, Lagace, DC, Ghose, S, Reister, R, Tannous, P, Green, T, Neve, RL, Chakravarty, S, Kumar, A, Eisch, AJ, Self, DW, Lee, FS, Tamminga, CA, Cooper, DC, Gershenfeld, HK & Nestler, EJ 2007, 'Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions', Cell, vol. 131, no. 2, pp. 391-404. https://doi.org/10.1016/j.cell.2007.09.018
Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ et al. Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions. Cell. 2007 Oct 19;131(2):391-404. https://doi.org/10.1016/j.cell.2007.09.018
Krishnan, Vaishnav ; Han, Ming Hu ; Graham, Danielle L. ; Berton, Olivier ; Renthal, William ; Russo, Scott J. ; LaPlant, Quincey ; Graham, Ami ; Lutter, Michael ; Lagace, Diane C. ; Ghose, Subroto ; Reister, Robin ; Tannous, Paul ; Green, Thomas ; Neve, Rachael L. ; Chakravarty, Sumana ; Kumar, Arvind ; Eisch, Amelia J. ; Self, David W. ; Lee, Francis S. ; Tamminga, Carol A. ; Cooper, Donald C. ; Gershenfeld, Howard K. ; Nestler, Eric J. / Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions. In: Cell. 2007 ; Vol. 131, No. 2. pp. 391-404.
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