CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits

Deanna L. Wallace, Ming Hu Han, Danielle L. Graham, Thomas Green, Vincent Vialou, Sergio D. Ĩiguez, Jun Li Cao, Anne Kirk, Sumana Chakravarty, Arvind Kumar, Vaishnav Krishnan, Rachael L. Neve, Don C. Cooper, Carlos A. Bolãos, Michel Barrot, Colleen A. McClung, Eric J. Nestler

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

Here, we characterized behavioral abnormalities induced by prolonged social isolation in adult rodents. Social isolation induced both anxiety- and anhedonia-like symptoms and decreased cAMP response element-binding protein (CREB) activity in the nucleus accumbens shell (NAcSh). All of these abnormalities were reversed by chronic, but not acute, antidepressant treatment. However, although the anxiety phenotype and its reversal by antidepressant treatment were CREB-dependent, the anhedonia-like symptoms were not mediated by CREB in NAcSh. We found that decreased CREB activity in NAcSh correlated with increased expression of certain K+ channels and reduced electrical excitability of NAcSh neurons, which was sufficient to induce anxiety-like behaviors and was reversed by chronic antidepressant treatment. Together, our results describe a model that distinguishes anxiety- and depression-like behavioral phenotypes, establish a selective role of decreased CREB activity in NAcSh in anxiety-like behavior, and provide a mechanism by which antidepressant treatment alleviates anxiety symptoms after social isolation.

Original languageEnglish (US)
Pages (from-to)200-209
Number of pages10
JournalNature Neuroscience
Volume12
Issue number2
DOIs
StatePublished - Feb 2009
Externally publishedYes

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Cyclic AMP Response Element-Binding Protein
Social Isolation
Nucleus Accumbens
Anxiety
Antidepressive Agents
Anhedonia
Phenotype
Rodentia
Depression
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wallace, D. L., Han, M. H., Graham, D. L., Green, T., Vialou, V., Ĩiguez, S. D., ... Nestler, E. J. (2009). CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. Nature Neuroscience, 12(2), 200-209. https://doi.org/10.1038/nn.2257

CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. / Wallace, Deanna L.; Han, Ming Hu; Graham, Danielle L.; Green, Thomas; Vialou, Vincent; Ĩiguez, Sergio D.; Cao, Jun Li; Kirk, Anne; Chakravarty, Sumana; Kumar, Arvind; Krishnan, Vaishnav; Neve, Rachael L.; Cooper, Don C.; Bolãos, Carlos A.; Barrot, Michel; McClung, Colleen A.; Nestler, Eric J.

In: Nature Neuroscience, Vol. 12, No. 2, 02.2009, p. 200-209.

Research output: Contribution to journalArticle

Wallace, DL, Han, MH, Graham, DL, Green, T, Vialou, V, Ĩiguez, SD, Cao, JL, Kirk, A, Chakravarty, S, Kumar, A, Krishnan, V, Neve, RL, Cooper, DC, Bolãos, CA, Barrot, M, McClung, CA & Nestler, EJ 2009, 'CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits', Nature Neuroscience, vol. 12, no. 2, pp. 200-209. https://doi.org/10.1038/nn.2257
Wallace, Deanna L. ; Han, Ming Hu ; Graham, Danielle L. ; Green, Thomas ; Vialou, Vincent ; Ĩiguez, Sergio D. ; Cao, Jun Li ; Kirk, Anne ; Chakravarty, Sumana ; Kumar, Arvind ; Krishnan, Vaishnav ; Neve, Rachael L. ; Cooper, Don C. ; Bolãos, Carlos A. ; Barrot, Michel ; McClung, Colleen A. ; Nestler, Eric J. / CREB regulation of nucleus accumbens excitability mediates social isolation-induced behavioral deficits. In: Nature Neuroscience. 2009 ; Vol. 12, No. 2. pp. 200-209.
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