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Nat Commun. 2015 May 8;6:7062. doi: 10.1038/ncomms8062.

Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.

Author information

1
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
2
Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, USA.
3
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
4
1] Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
5
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA.
6
Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA
7
Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.

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.

PMID:
25952660
PMCID:
PMC4430111
DOI:
10.1038/ncomms8062
[Indexed for MEDLINE]
Free PMC Article

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