title: Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression.
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.
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Bagot
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Parise
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Peña
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Hong-Xing
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ian
authors.initials: I
authors.lastname: Maze
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Dipesh
authors.initials: D
authors.lastname: Chaudhury
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Persaud
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland, 21201, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Cachope
authors.affiliation: Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bolaños-Guzmán
authors.affiliation: Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cheer
authors.affiliation: Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cheer
authors.affiliation: Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.affiliation: 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.
authors.forename: Ming-Hu
authors.initials: MH
authors.lastname: Han
authors.affiliation: Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D002908:Chronic Disease; D003863:Depression / Q000503:physiopathology*; D004198:Disease Susceptibility / Q000503:physiopathology; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000503:physiopathology*; D036881:Long-Term Synaptic Depression; D008297:Male; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000473:pathology*; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017397:Prefrontal Cortex; D012919:Social Behavior; D013315:Stress, Psychological / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission