Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Abstract

Enhanced glutamatergic transmission in the nucleus accumbens (NAc) has been implicated in the pathophysiology of depression, yet the underlying source is not known. Here, the authors demonstrate a unique role for ventral hippocampal-NAc glutamatergic projections in regulating depression-like behaviour.

Related collections

Most cited references 36

Record: found
Abstract: found
Article: not found

Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

Olivier Berton, Colleen A. McClung, Ralph J Dileone … (2006)

Mice experiencing repeated aggression develop a long-lasting aversion to social contact, which can be normalized by chronic, but not acute, administration of antidepressant. Using viral-mediated, mesolimbic dopamine pathway-specific knockdown of brain-derived neurotrophic factor (BDNF), we showed that BDNF is required for the development of this experience-dependent social aversion. Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant. These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences.

0 comments Cited 543 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Rapid regulation of depression-related behaviors by control of midbrain dopamine neurons

Dipesh Chaudhury, Jessica Walsh, Allyson K. Friedman … (2012)

Ventral tegmental area (VTA) dopamine (DA) neurons in the brain’s reward circuit play a crucial role in mediating stress responses 1–4 including determining susceptibility vs. resilience to social stress-induced behavioural abnormalities 5 . VTA DA neurons exhibit two in vivo patterns of firing: low frequency tonic firing and high frequency phasic firing 6–8 . Phasic firing of the neurons, which is well known to encode reward signals 6,7,9 , is upregulated by repeated social defeat stress, a highly validated mouse model of depression 5,8,10–13 . Surprisingly, this pathophysiological effect is seen in susceptible mice only, with no change in firing rate apparent in resilient individuals 5,8 . However, direct evidence linking—in real-time—DA neuron phasic firing in promoting the susceptible (depression-like) phenotype is lacking. Here, we took advantage of the temporal precision and cell type- and projection pathway-specificity of optogenetics to demonstrate that enhanced phasic firing of these neurons mediates susceptibility to social defeat stress in freely behaving mice. We show that optogenetic induction of phasic, but not tonic, firing, in VTA DA neurons of mice undergoing a subthreshold social defeat paradigm rapidly induced a susceptible phenotype as measured by social avoidance and decreased sucrose preference. Optogenetic phasic stimulation of these neurons also quickly induced a susceptible phenotype in previously resilient mice that had been subjected to repeated social defeat stress. Furthermore, we show differences in projection pathway-specificity in promoting stress susceptibility: phasic activation of VTA neurons projecting to the nucleus accumbens (NAc), but not to the medial prefrontal cortex (mPFC), induced susceptibility to social defeat stress. Conversely, optogenetic inhibition of the VTA-NAc projection induced resilience, while inhibition of the VTA-mPFC projection promoted susceptibility. Overall, these studies reveal novel firing pattern- and neural circuit-specific mechanisms of depression.

0 comments Cited 351 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic.

Kerry J Ressler, Helen Mayberg (2007)

Recent decades have witnessed tremendous advances in the neuroscience of emotion, learning and memory, and in animal models for understanding depression and anxiety. This review focuses on new rationally designed psychiatric treatments derived from preclinical human and animal studies. Nonpharmacological treatments that affect disrupted emotion circuits include vagal nerve stimulation, rapid transcranial magnetic stimulation and deep brain stimulation, all borrowed from neurological interventions that attempt to target known pathological foci. Other approaches include drugs that are given in relation to specific learning events to enhance or disrupt endogenous emotional learning processes. Imaging data suggest that common regions of brain activation are targeted with pharmacological and somatic treatments as well as with the emotional learning in psychotherapy. Although many of these approaches are experimental, the rapidly developing understanding of emotional circuit regulation is likely to provide exciting and powerful future treatments for debilitating mood and anxiety disorders.

0 comments Cited 257 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Nat Commun

Journal ID (iso-abbrev): Nat Commun

Title: Nature Communications

Publisher: Nature Pub. Group

ISSN (Electronic): 2041-1723

Publication date (Electronic): 08 May 2015

Volume: 6

Electronic Location Identifier: 7062

Affiliations

[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 ]Department of Anatomy and Neurobiology, University of Maryland School of Medicine , Baltimore, Maryland, 21201, USA

[5 ]Departments of Bioengineering and Psychiatry and Behavioral Sciences, Stanford University , Stanford, California 94305, USA

Author notes

[a ] eric.nestler@ 123456mssm.edu

[*]

These authors contributed equally to this work.

Article

Publisher Item ID: ncomms8062

DOI: 10.1038/ncomms8062

PMC ID: 4430111

PubMed ID: 25952660

SO-VID: 9057cd7d-a524-469b-989b-4a19c5f49d84

License:

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

History

Date received : 14 December 2014

Date accepted : 26 March 2015

Comments

Comment on this article

scite_

Cited by 162

See all cited by

Most referenced authors 485

See all reference authors

- Version 1

Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

Read this article at

Abstract

Abstract

Related collections

Measurement of Glucocorticoid Receptor Signaling in Major Depression

Most cited references 36

Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress.

Rapid regulation of depression-related behaviors by control of midbrain dopamine neurons

Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 443

Cited by 162

Most referenced authors 485