Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

Rosemary C. Bagot, Eric M. Parise, Catherine J. Peña, Hong Xing Zhang, Ian Maze, Dipesh Chaudhury, Brianna Persaud, Roger Cachope, Carlos A. Bolaños-Guzmán, Joseph Cheer, Karl Deisseroth, Ming Hu Han, Eric J. Nestler

Research output: Contribution to journalArticle

Abstract

Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated in the pathophysiology of depression; however, the afferent source of this increased glutamate tone is not known. The NAc receives glutamatergic inputs from the medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) and basolateral amygdala (AMY). Here, we demonstrate that glutamatergic vHIP afferents to NAc regulate susceptibility to chronic social defeat stress (CSDS). We observe reduced activity in vHIP in mice resilient to CSDS. Furthermore, attenuation of vHIP-NAc transmission by optogenetic induction of long-term depression is pro-resilient, whereas acute enhancement of this input is pro-susceptible. This effect is specific to vHIP afferents to the NAc, as optogenetic stimulation of either mPFC or AMY afferents to the NAc is pro-resilient. These data indicate that vHIP afferents to NAc uniquely regulate susceptibility to CSDS, highlighting an important, novel circuit-specific mechanism in depression.

Original languageEnglish (US)
Article number7062
JournalNature communications
Volume6
DOIs
StatePublished - May 8 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Bagot, R. C., Parise, E. M., Peña, C. J., Zhang, H. X., Maze, I., Chaudhury, D., Persaud, B., Cachope, R., Bolaños-Guzmán, C. A., Cheer, J., Deisseroth, K., Han, M. H., & Nestler, E. J. (2015). Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nature communications, 6, [7062]. https://doi.org/10.1038/ncomms8062