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Neuronal correlates of depression

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Abstract

Major depressive disorder (MDD) is a common psychiatric disorder effecting approximately 121 million people worldwide and recent reports from the World Health Organization (WHO) suggest that it will be the leading contributor to the global burden of diseases. At present, the most commonly used treatment strategies are still based on the monoamine hypothesis that has been the predominant theory in the last 60 years. Clinical observations show that only a subset of depressed patients exhibits full remission when treated with classical monoamine-based antidepressants together with the fact that patients exhibit multiple symptoms suggest that the pathophysiology leading to mood disorders may differ between patients. Accumulating evidence indicates that depression is a neural circuit disorder and that onset of depression may be located at different regions of the brain involving different transmitter systems and molecular mechanisms. This review synthesises findings from rodent studies from which emerges a role for different, yet interconnected, molecular systems and associated neural circuits to the aetiology of depression.

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Abbreviations

3V:

Third ventricle

4V:

Fourth ventricle

5-HT:

Serotonin

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Arc:

Activity-regulated cytoskeleton-associated protein gene

BDNF:

Brain-derived neurotrophic factor

BLA:

Basolateral amygdala

Ca2+ :

Calcium

CaMKII:

Calcium/calmodulin-dependent protein kinase II

CeM:

Central amygdala

CPP:

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid

CRF:

Corticortrophin-releasing factor

CSD:

Chronic social defeat

CUS:

Chronic unpredictable stress

D1:

Dopamine 1 receptor

D2:

Dopamine 2 receptor

D3V:

Dorsal third ventricle

DBS:

Deep brain stimulation

delta FosB:

Delta FBJ murine osteosarcoma viral oncogene homolog B

DMH:

Dorsomedial nucleus of the hypothalamus

DNMT:

DNA methyltransferase

DRN:

Dorsal raphe nucleus

eEF2:

Eukaryotic elongation factor

Egr1:

Early growth response protein 1 gene

ERK1/2:

Extracellular signal regulated kinase

FosB:

FBJ murine osteosarcoma viral oncogene homolog B

G9a:

Histone H3 lysine 9 methyltransferase

GABA:

Gamma-aminobutyric acid

GLP:

Histone H3 lysine 9 methyltransferase

GluR1:

Glutamate receptor subunit 1

GluR2:

Glutamate receptor subunit 2

GluR3:

Glutamate receptor subunit 3

GPo:

Globus pallidum

H3K9me2:

Histone H3 dimethyl Lys9

HATS:

Histone acetyltransferase

HCN:

Hyperpolarisation-activated cyclic nucleotide-gated channel

HDAC:

Histone deacetylase

HDM:

Histone demethylase

HMT:

Histone methyltransferase

I h :

Hyperpolarisation-activated non-selective cation current

IKK:

IKB kinase

IKKdn:

IKK dominant negative

IVF:

In vitro fertilisation

K+ :

Potassium

LC:

Locus coeruleus

LDTg:

Laterodorsal tegmental nucleus

LH:

Lateral hypothalamus

LHb:

Lateral habenula

LTD:

Laterodorsal tegmentum

MAPK:

Mitogen-activated protein kinases

MDD:

Major depressive disorder

mGluR2:

Metabotropic glutamate receptor 2

MK-801:

5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine

mper1/2:

Period gene 1 and 2

mPFC:

Medial prefrontal cortex

MSN:

Medium spiny neurons

mTOR:

Mammalian target of rapamycin

NAc:

Nucleus accumbens

NFkB :

Nuclear factor kB

NMDAR:

N-methyl-d-aspartate receptor

NR2B:

NMDAR 2B subunit

PPTg:

Pedunculopontine tegmental nucleus

REM:

Rapid eye movement

RMTg:

Rostromedial tegmental nucleus

SC1:

Sparc-like 1

SCN:

Suprachiasmatic nucleus

SD:

Sleep deprivation

SDT:

Sleep deprivation therapy

SN:

Substrantia nigra

SPZ:

Subparaventricular zone

SSRI:

Serotonin selective reuptake inhibitor

SUV39H1:

Histone-lysine N-methyltransferase

vHIP:

Ventral hippocampus

VP:

Ventral pallidum

VSCC:

Voltage sensitive calcium channels

VTA:

Ventral tegmental area

WKY:

Wistar Kyoto

ZFP:

Zing-finger protein

References

  1. Ferrari AJ, Charlson FJ, Norman RE, Flaxman AD, Patten SB, Vos T, Whiteford HA (2013) The epidemiological modelling of major depressive disorder: application for the Global Burden of Disease Study 2010. PLoS One 8:e69637. doi:10.1371/journal.pone.0069637

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, Charlson FJ, Norman RE, Flaxman AD, Johns N, Burstein R, Murray CJ, Vos T (2013) Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382:1575–1586. doi:10.1016/S0140-6736(13)61611-6

    Article  PubMed  Google Scholar 

  3. Toseeb U, Brage S, Corder K, Dunn VJ, Jones PB, Owens M, St Clair MC, van Sluijs EM, Goodyer IM (2014) Exercise and depressive symptoms in adolescents: a longitudinal cohort study. JAMA Pediatrics 168:1093–1100. doi:10.1001/jamapediatrics.2014.1794

    Article  PubMed  Google Scholar 

  4. Nestler EJ (1998) Antidepressant treatments in the 21st century. Biol Psychiatry 44:526–533. pii: S000632239800095X

  5. Hyman SE (2014) Revitalizing psychiatric therapeutics. Neuropsychopharmacology 39:220–229. doi:10.1038/npp.2013.181

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151. doi:10.1038/nrn1846

    Article  CAS  PubMed  Google Scholar 

  7. Mathew SJ, Manji HK, Charney DS (2008) Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 33:2080–2092. doi:10.1038/sj.npp.1301652

    Article  CAS  PubMed  Google Scholar 

  8. Mayberg HS (2009) Targeted electrode-based modulation of neural circuits for depression. J Clin Invest 119:717–725. doi:10.1172/JCI38454

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Holtzheimer PE 3rd, Mayberg HS (2010) Deep brain stimulation for treatment-resistant depression. Am J Psychiatry 167:1437–1444. doi:10.1176/appi.ajp.2010.10010141

    Article  PubMed Central  PubMed  Google Scholar 

  10. Zarate C, Duman RS, Liu G, Sartori S, Quiroz J, Murck H (2013) New paradigms for treatment-resistant depression. Ann N Y Acad Sci 1292:21–31. doi:10.1111/nyas.12223

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Merkl A, Neumann WJ, Huebl J, Aust S, Horn A, Krauss JK, Dziobek I, Kuhn J, Schneider GH, Bajbouj M, Kuhn AA (2015) Modulation of beta-band activity in the subgenual anterior cingulate cortex during emotional empathy in treatment-resistant depression. Cereb Cortex. doi:10.1093/cercor/bhv100

    PubMed  Google Scholar 

  12. Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, Graham A, Lutter M, Lagace DC, Ghose S, Reister R, Tannous P, Green TA, Neve RL, Chakravarty S, Kumar A, Eisch AJ, Self DW, Lee FS, Tamminga CA, Cooper DC, Gershenfeld HK, Nestler EJ (2007) Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131:391–404. doi:10.1016/j.cell.2007.09.018

    Article  CAS  PubMed  Google Scholar 

  13. Sutton MA, Taylor AM, Ito HT, Pham A, Schuman EM (2007) Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis. Neuron 55:648–661. doi:10.1016/j.neuron.2007.07.030

    Article  CAS  PubMed  Google Scholar 

  14. Christoffel DJ, Golden SA, Dumitriu D, Robison AJ, Janssen WG, Ahn HF, Krishnan V, Reyes CM, Han MH, Ables JL, Eisch AJ, Dietz DM, Ferguson D, Neve RL, Greengard P, Kim Y, Morrison JH, Russo SJ (2011) IkappaB kinase regulates social defeat stress-induced synaptic and behavioral plasticity. J Neurosci 31:314–321. doi:10.1523/JNEUROSCI.4763-10.2011

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Russo SJ, Nestler EJ (2013) The brain reward circuitry in mood disorders. Nat Rev Neurosci 14:609–625. doi:10.1038/nrn3381

    Article  CAS  PubMed  Google Scholar 

  16. Chandley MJ, Szebeni A, Szebeni K, Crawford JD, Stockmeier CA, Turecki G, Kostrzewa RM, Ordway GA (2014) Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression. Int J Neuropsychopharmacol 17:1569–1578. doi:10.1017/S1461145714000662

    Article  CAS  PubMed  Google Scholar 

  17. Lopizzo N, Bocchio Chiavetto L, Cattane N, Plazzotta G, Tarazi FI, Pariante CM, Riva MA, Cattaneo A (2015) Gene-environment interaction in major depression: focus on experience-dependent biological systems. Frontiers in psychiatry 6:68. doi:10.3389/fpsyt.2015.00068

    Article  PubMed Central  PubMed  Google Scholar 

  18. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM (2002) Neurobiology of depression. Neuron 34:13–25. pii: S0896627302006530

  19. Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14:7–23. doi:10.1038/nrn3379

    Article  CAS  PubMed  Google Scholar 

  20. Berton O, McClung CA, Dileone RJ, Krishnan V, Renthal W, Russo SJ, Graham D, Tsankova NM, Bolanos CA, Rios M, Monteggia LM, Self DW, Nestler EJ (2006) Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress. Science 311:864–868. doi:10.1126/science.1120972

    Article  CAS  PubMed  Google Scholar 

  21. Walsh JJ, Friedman AK, Sun H, Heller EA, Ku SM, Juarez B, Burnham VL, Mazei-Robison MS, Ferguson D, Golden SA, Koo JW, Chaudhury D, Christoffel DJ, Pomeranz L, Friedman JM, Russo SJ, Nestler EJ, Han MH (2014) Stress and CRF gate neural activation of BDNF in the mesolimbic reward pathway. Nat Neurosci 17:27–29. doi:10.1038/nn.3591

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Lemos JC, Wanat MJ, Smith JS, Reyes BA, Hollon NG, Van Bockstaele EJ, Chavkin C, Phillips PE (2012) Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive. Nature 490:402–406. doi:10.1038/nature11436

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Pecina S, Schulkin J, Berridge KC (2006) Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress? BMC Biol 4:8. doi:10.1186/1741-7007-4-8

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Yu H, Chen ZY (2011) The role of BDNF in depression on the basis of its location in the neural circuitry. Acta Pharmacol Sin 32:3–11. doi:10.1038/aps.2010.184

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Autry AE, Monteggia LM (2012) Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258. doi:10.1124/pr.111.005108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Pizarro JM, Lumley LA, Medina W, Robison CL, Chang WE, Alagappan A, Bah MJ, Dawood MY, Shah JD, Mark B, Kendall N, Smith MA, Saviolakis GA, Meyerhoff JL (2004) Acute social defeat reduces neurotrophin expression in brain cortical and subcortical areas in mice. Brain Res 1025:10–20. doi:10.1016/j.brainres.2004.06.085

    Article  CAS  PubMed  Google Scholar 

  27. Fanous S, Hammer RP Jr, Nikulina EM (2010) Short- and long-term effects of intermittent social defeat stress on brain-derived neurotrophic factor expression in mesocorticolimbic brain regions. Neuroscience 167:598–607. doi:10.1016/j.neuroscience.2010.02.064

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Guilloux JP, Douillard-Guilloux G, Kota R, Wang X, Gardier AM, Martinowich K, Tseng GC, Lewis DA, Sibille E (2012) Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with major depression. Mol Psychiatry 17:1130–1142. doi:10.1038/mp.2011.113

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50:260–265

    Article  CAS  PubMed  Google Scholar 

  30. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60:804–815. doi:10.1001/archpsyc.60.8.804

    Article  CAS  PubMed  Google Scholar 

  31. Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R (2005) Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol Brain Res 136:29–37. doi:10.1016/j.molbrainres.2004.12.020

    Article  CAS  PubMed  Google Scholar 

  32. Duclot F, Kabbaj M (2015) Epigenetic mechanisms underlying the role of brain-derived neurotrophic factor in depression and response to antidepressants. J Exp Biol 218:21–31. doi:10.1242/jeb.107086

    Article  PubMed  PubMed Central  Google Scholar 

  33. Chourbaji S, Brandwein C, Gass P (2011) Altering BDNF expression by genetics and/or environment: impact for emotional and depression-like behaviour in laboratory mice. Neurosci Biobehav Rev 35:599–611. doi:10.1016/j.neubiorev.2010.07.003

    Article  CAS  PubMed  Google Scholar 

  34. Tapia-Arancibia L, Rage F, Givalois L, Arancibia S (2004) Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 25:77–107. doi:10.1016/j.yfrne.2004.04.001

    Article  CAS  PubMed  Google Scholar 

  35. Cai S, Huang S, Hao W (2015) New hypothesis and treatment targets of depression: an integrated view of key findings. Neurosci Bull 31:61–74. doi:10.1007/s12264-014-1486-4

    Article  PubMed  Google Scholar 

  36. Suenaga T, Morinobu S, Kawano K, Sawada T, Yamawaki S (2004) Influence of immobilization stress on the levels of CaMKII and phospho-CaMKII in the rat hippocampus. Int J Neuropsychopharmacol 7:299–309. doi:10.1017/S1461145704004304

    Article  CAS  PubMed  Google Scholar 

  37. Almeida RC, Souza DG, Soletti RC, Lopez MG, Rodrigues AL, Gabilan NH (2006) Involvement of PKA, MAPK/ERK and CaMKII, but not PKC in the acute antidepressant-like effect of memantine in mice. Neurosci Lett 395:93–97. doi:10.1016/j.neulet.2005.10.057

    Article  CAS  PubMed  Google Scholar 

  38. Robison AJ, Vialou V, Sun HS, Labonte B, Golden SA, Dias C, Turecki G, Tamminga C, Russo S, Mazei-Robison M, Nestler EJ (2014) Fluoxetine epigenetically alters the CaMKIIalpha promoter in nucleus accumbens to regulate DeltaFosB binding and antidepressant effects. Neuropsychopharmacology 39:1178–1186. doi:10.1038/npp.2013.319

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Thiagarajan TC, Piedras-Renteria ES, Tsien RW (2002) alpha- and betaCaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron 36:1103–1114

    Article  CAS  PubMed  Google Scholar 

  40. Meye FJ, Lecca S, Valentinova K, Mameli M (2013) Synaptic and cellular profile of neurons in the lateral habenula. Front Hum Neurosci 7:860. doi:10.3389/fnhum.2013.00860

    Article  PubMed Central  PubMed  Google Scholar 

  41. Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, Henn FA, Meyer-Lindenberg A (2010) Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry 67:e9–e11. doi:10.1016/j.biopsych.2009.08.027

    Article  PubMed  Google Scholar 

  42. Aizawa H, Cui W, Tanaka K, Okamoto H (2013) Hyperactivation of the habenula as a link between depression and sleep disturbance. Front Hum Neurosci 7:826. doi:10.3389/fnhum.2013.00826

    Article  PubMed Central  PubMed  Google Scholar 

  43. Li B, Piriz J, Mirrione M, Chung C, Proulx CD, Schulz D, Henn F, Malinow R (2011) Synaptic potentiation onto habenula neurons in the learned helplessness model of depression. Nature 470:535–539. doi:10.1038/nature09742

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F, Malinow R, Yates JR 3rd, Hu H (2013) betaCaMKII in lateral habenula mediates core symptoms of depression. Science 341:1016–1020. doi:10.1126/science.1240729

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47:351–354. pii: S0006-3223(99)00230-9

  46. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63:856–864. doi:10.1001/archpsyc.63.8.856

    Article  CAS  PubMed  Google Scholar 

  47. Price RB, Nock MK, Charney DS, Mathew SJ (2009) Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 66:522–526. doi:10.1016/j.biopsych.2009.04.029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475:91–95. doi:10.1038/nature10130

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Dwyer JM, Lepack AE, Duman RS (2013) mGluR2/3 blockade produces rapid and long-lasting reversal of anhedonia caused by chronic stress exposure. J Mol Psychiatry 1:15. doi:10.1186/2049-9256-1-15

    Article  PubMed Central  PubMed  Google Scholar 

  50. Iadarola ND, Niciu MJ, Richards EM, Vande Voort JL, Ballard ED, Lundin NB, Nugent AC, Machado-Vieira R, Zarate CA Jr (2015) Ketamine and other N-methyl-d-aspartate receptor antagonists in the treatment of depression: a perspective review. Ther Adv Chronic Dis 6:97–114. doi:10.1177/2040622315579059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Gideons ES, Kavalali ET, Monteggia LM (2014) Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses. Proc Natl Acad Sci USA 111:8649–8654. doi:10.1073/pnas.1323920111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Nosyreva E, Szabla K, Autry AE, Ryazanov AG, Monteggia LM, Kavalali ET (2013) Acute suppression of spontaneous neurotransmission drives synaptic potentiation. J Neurosci 33:6990–7002. doi:10.1523/JNEUROSCI.4998-12.2013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63:349–352. doi:10.1016/j.biopsych.2007.05.028

    Article  CAS  PubMed  Google Scholar 

  54. Hou L, Klann E (2004) Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 24:6352–6361. doi:10.1523/JNEUROSCI.0995-04.2004

    Article  CAS  PubMed  Google Scholar 

  55. Gong R, Park CS, Abbassi NR, Tang SJ (2006) Roles of glutamate receptors and the mammalian target of rapamycin (mTOR) signaling pathway in activity-dependent dendritic protein synthesis in hippocampal neurons. J Biol Chem 281:18802–18815. doi:10.1074/jbc.M512524200

    Article  CAS  PubMed  Google Scholar 

  56. Yu JJ, Zhang Y, Wang Y, Wen ZY, Liu XH, Qin J, Yang JL (2013) Inhibition of calcineurin in the prefrontal cortex induced depressive-like behavior through mTOR signaling pathway. Psychopharmacology 225:361–372. doi:10.1007/s00213-012-2823-9

    Article  CAS  PubMed  Google Scholar 

  57. Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18:1926–1945. doi:10.1101/gad.1212704

    Article  CAS  PubMed  Google Scholar 

  58. Duman RS, Li N, Liu RJ, Duric V, Aghajanian G (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology 62:35–41. doi:10.1016/j.neuropharm.2011.08.044

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Abdallah CG, Sanacora G, Duman RS, Krystal JH (2015) Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med 66:509–523. doi:10.1146/annurev-med-053013-062946

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS (2012) Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nat Med 18:1413–1417. doi:10.1038/nm.2886

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Bessa JM, Ferreira D, Melo I, Marques F, Cerqueira JJ, Palha JA, Almeida OF, Sousa N (2009) The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling. Mol Psychiatry 14(764–773):739. doi:10.1038/mp.2008.119

    Article  CAS  Google Scholar 

  62. Yuen EY, Wei J, Liu W, Zhong P, Li X, Yan Z (2012) Repeated stress causes cognitive impairment by suppressing glutamate receptor expression and function in prefrontal cortex. Neuron 73:962–977. doi:10.1016/j.neuron.2011.12.033

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. Bessa JM, Morais M, Marques F, Pinto L, Palha JA, Almeida OF, Sousa N (2013) Stress-induced anhedonia is associated with hypertrophy of medium spiny neurons of the nucleus accumbens. Transl Psychiatry 3:e266. doi:10.1038/tp.2013.39

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  64. Vyas A, Pillai AG, Chattarji S (2004) Recovery after chronic stress fails to reverse amygdaloid neuronal hypertrophy and enhanced anxiety-like behavior. Neuroscience 128:667–673. doi:10.1016/j.neuroscience.2004.07.013

    Article  CAS  PubMed  Google Scholar 

  65. Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol Psychiatry 59:1116–1127. doi:10.1016/j.biopsych.2006.02.013

    Article  CAS  PubMed  Google Scholar 

  66. Ota KT, Liu RJ, Voleti B, Maldonado-Aviles JG, Duric V, Iwata M, Dutheil S, Duman C, Boikess S, Lewis DA, Stockmeier CA, DiLeone RJ, Rex C, Aghajanian GK, Duman RS (2014) REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nat Med 20:531–535. doi:10.1038/nm.3513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Liu RJ, Fuchikami M, Dwyer JM, Lepack AE, Duman RS, Aghajanian GK (2013) GSK-3 inhibition potentiates the synaptogenic and antidepressant-like effects of subthreshold doses of ketamine. Neuropsychopharmacology 38:2268–2277. doi:10.1038/npp.2013.128

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329:959–964. doi:10.1126/science.1190287

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Liu RJ, Lee FS, Li XY, Bambico F, Duman RS, Aghajanian GK (2012) Brain-derived neurotrophic factor Val66Met allele impairs basal and ketamine-stimulated synaptogenesis in prefrontal cortex. Biol Psychiatry 71:996–1005. doi:10.1016/j.biopsych.2011.09.030

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Jourdi H, Hsu YT, Zhou M, Qin Q, Bi X, Baudry M (2009) Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation. J Neurosci 29:8688–8697. doi:10.1523/JNEUROSCI.6078-08.2009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  71. Lepack AE, Fuchikami M, Dwyer JM, Banasr M, Duman RS (2015) BDNF release is required for the behavioral actions of ketamine. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyu033

    PubMed Central  Google Scholar 

  72. Hasler G, Drevets WC, Manji HK, Charney DS (2004) Discovering endophenotypes for major depression. Neuropsychopharmacology 29:1765–1781. doi:10.1038/sj.npp.1300506

    Article  CAS  PubMed  Google Scholar 

  73. Lamers F, Vogelzangs N, Merikangas KR, de Jonge P, Beekman AT, Penninx BW (2013) Evidence for a differential role of HPA-axis function, inflammation and metabolic syndrome in melancholic versus atypical depression. Mol Psychiatry 18:692–699. doi:10.1038/mp.2012.144

    Article  CAS  PubMed  Google Scholar 

  74. Sotnikov S, Wittmann A, Bunck M, Bauer S, Deussing J, Schmidt M, Touma C, Landgraf R, Czibere L (2014) Blunted HPA axis reactivity reveals glucocorticoid system dysbalance in a mouse model of high anxiety-related behavior. Psychoneuroendocrinology 48:41–51. doi:10.1016/j.psyneuen.2014.06.006

    Article  CAS  PubMed  Google Scholar 

  75. Santana MM, Rosmaninho-Salgado J, Cortez V, Pereira FC, Kaster MP, Aveleira CA, Ferreira M, Alvaro AR, Cavadas C (2015) Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress. Eur Neuropsychopharmacol. doi:10.1016/j.euroneuro.2015.06.013

    PubMed  Google Scholar 

  76. Holsboer F, Barden N (1996) Antidepressants and hypothalamic–pituitary–adrenocortical regulation. Endocr Rev 17:187–205. doi:10.1210/edrv-17-2-187

    Article  CAS  PubMed  Google Scholar 

  77. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269–301. doi:10.1210/edrv.19.3.0331

    PubMed  Google Scholar 

  78. Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477–501. doi:10.1016/S0893-133X(00)00159-7

    Article  CAS  PubMed  Google Scholar 

  79. Chang HS, Won ES, Lee HY, Ham BJ, Kim YG, Lee MS (2015) The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events. J Neural Transm 122:59–68. doi:10.1007/s00702-014-1333-9

    Article  CAS  PubMed  Google Scholar 

  80. Banki CM, Bissette G, Arato M, O’Connor L, Nemeroff CB (1987) CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia. Am J Psychiatry 144:873–877

    Article  CAS  PubMed  Google Scholar 

  81. Bissette G, Klimek V, Pan J, Stockmeier C, Ordway G (2003) Elevated concentrations of CRF in the locus coeruleus of depressed subjects. Neuropsychopharmacology 28:1328–1335. doi:10.1038/sj.npp.1300191

    Article  CAS  PubMed  Google Scholar 

  82. Merali Z, Kent P, Du L, Hrdina P, Palkovits M, Faludi G, Poulter MO, Bedard T, Anisman H (2006) Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects. Biol Psychiatry 59:594–602. doi:10.1016/j.biopsych.2005.08.008

    Article  CAS  PubMed  Google Scholar 

  83. Lloyd RB, Nemeroff CB (2011) The role of corticotropin-releasing hormone in the pathophysiology of depression: therapeutic implications. Curr Top Med Chem 11:609–617

    Article  CAS  PubMed  Google Scholar 

  84. Plotsky PM, Thrivikraman KV, Nemeroff CB, Caldji C, Sharma S, Meaney MJ (2005) Long-term consequences of neonatal rearing on central corticotropin-releasing factor systems in adult male rat offspring. Neuropsychopharmacology 30:2192–2204. doi:10.1038/sj.npp.1300769

    Article  CAS  PubMed  Google Scholar 

  85. Antunes MS, Ruff JR, de Oliveira Espinosa D, Piegas MB, de Brito ML, Rocha KA, de Gomes MG, Goes AT, Souza LC, Donato F, Boeira SP, Jesse CR (2015) Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice. Horm Behav 73:56–63. doi:10.1016/j.yhbeh.2015.05.018

    Article  CAS  PubMed  Google Scholar 

  86. McEwen BS (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873–904. doi:10.1152/physrev.00041.2006

    Article  PubMed  Google Scholar 

  87. McEwen BS, Gray JD, Nasca C (2015) 60 years of neuroendocrinology: redefining neuroendocrinology: stress, sex and cognitive and emotional regulation. J Endocrinol 226:T67–T83. doi:10.1530/JOE-15-0121

    Article  CAS  PubMed  Google Scholar 

  88. Datson NA, van den Oever JM, Korobko OB, Magarinos AM, de Kloet ER, McEwen BS (2013) Previous history of chronic stress changes the transcriptional response to glucocorticoid challenge in the dentate gyrus region of the male rat hippocampus. Endocrinology 154:3261–3272. doi:10.1210/en.2012-2233

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Nasca C, Xenos D, Barone Y, Caruso A, Scaccianoce S, Matrisciano F, Battaglia G, Mathe AA, Pittaluga A, Lionetto L, Simmaco M, Nicoletti F (2013) l-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci USA 110:4804–4809. doi:10.1073/pnas.1216100110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  90. Nasca C, Bigio B, Zelli D, Nicoletti F, McEwen BS (2015) Mind the gap: glucocorticoids modulate hippocampal glutamate tone underlying individual differences in stress susceptibility. Mol Psychiatry 20:755–763. doi:10.1038/mp.2014.96

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  91. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609. doi:10.1073/pnas.0500398102

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Kessler RC (1997) The effects of stressful life events on depression. Annu Rev Psychol 48:191–214. doi:10.1146/annurev.psych.48.1.191

    Article  CAS  PubMed  Google Scholar 

  93. Hammen C (2005) Stress and depression. Annu Rev Clin Psychol 1:293–319. doi:10.1146/annurev.clinpsy.1.102803.143938

    Article  PubMed  Google Scholar 

  94. Dudley KJ, Li X, Kobor MS, Kippin TE, Bredy TW (2011) Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders. Neurosci Biobehav Rev 35:1544–1551. doi:10.1016/j.neubiorev.2010.12.016

    Article  PubMed  Google Scholar 

  95. Vialou V, Feng J, Robison AJ, Nestler EJ (2013) Epigenetic mechanisms of depression and antidepressant action. Annu Rev Pharmacol Toxicol 53:59–87. doi:10.1146/annurev-pharmtox-010611-134540

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Nestler EJ (2014) Epigenetic mechanisms of depression. JAMA Psychiatry 71:454–456. doi:10.1001/jamapsychiatry.2013.4291

    Article  PubMed Central  PubMed  Google Scholar 

  97. Sun H, Kennedy PJ, Nestler EJ (2013) Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology 38:124–137. doi:10.1038/npp.2012.73

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  98. Covington HE 3rd, Maze I, LaPlant QC, Vialou VF, Ohnishi YN, Berton O, Fass DM, Renthal W, Rush AJ 3rd, Wu EY, Ghose S, Krishnan V, Russo SJ, Tamminga C, Haggarty SJ, Nestler EJ (2009) Antidepressant actions of histone deacetylase inhibitors. J Neurosci 29:11451–11460. doi:10.1523/JNEUROSCI.1758-09.2009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Uchida S, Hara K, Kobayashi A, Otsuki K, Yamagata H, Hobara T, Suzuki T, Miyata N, Watanabe Y (2011) Epigenetic status of Gdnf in the ventral striatum determines susceptibility and adaptation to daily stressful events. Neuron 69:359–372. doi:10.1016/j.neuron.2010.12.023

    Article  CAS  PubMed  Google Scholar 

  100. Renthal W, Maze I, Krishnan V, Covington HE 3rd, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ (2007) Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 56:517–529. doi:10.1016/j.neuron.2007.09.032

    Article  CAS  PubMed  Google Scholar 

  101. Liu D, Qiu HM, Fei HZ, Hu XY, Xia HJ, Wang LJ, Qin LJ, Jiang XH, Zhou QX (2014) Histone acetylation and expression of mono-aminergic transmitters synthetases involved in CUS-induced depressive rats. Exp Biol Med (Maywood) 239:330–336. doi:10.1177/1535370213513987

    Article  CAS  Google Scholar 

  102. Covington HE 3rd, Vialou VF, LaPlant Q, Ohnishi YN, Nestler EJ (2011) Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci Lett 493:122–126. doi:10.1016/j.neulet.2011.02.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  103. Covington HE 3rd, Maze I, Sun H, Bomze HM, DeMaio KD, Wu EY, Dietz DM, Lobo MK, Ghose S, Mouzon E, Neve RL, Tamminga CA, Nestler EJ (2011) A role for repressive histone methylation in cocaine-induced vulnerability to stress. Neuron 71:656–670. doi:10.1016/j.neuron.2011.06.007

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Heller EA, Cates HM, Pena CJ, Sun H, Shao N, Feng J, Golden SA, Herman JP, Walsh JJ, Mazei-Robison M, Ferguson D, Knight S, Gerber MA, Nievera C, Han MH, Russo SJ, Tamminga CS, Neve RL, Shen L, Zhang HS, Zhang F, Nestler EJ (2014) Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors. Nat Neurosci 17:1720–1727. doi:10.1038/nn.3871

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Nghia NA, Hirasawa T, Kasai H, Obata C, Moriishi K, Mochizuki K, Koizumi S, Kubota T (2015) Long-term imipramine treatment increases N-methyl-d-aspartate receptor activity and expression via epigenetic mechanisms. Eur J Pharmacol 752:69–77. doi:10.1016/j.ejphar.2015.02.010

    Article  CAS  PubMed  Google Scholar 

  106. Dell’Osso B, D’Addario C, Carlotta Palazzo M, Benatti B, Camuri G, Galimberti D, Fenoglio C, Scarpini E, Di Francesco A, Maccarrone M, Altamura AC (2014) Epigenetic modulation of BDNF gene: differences in DNA methylation between unipolar and bipolar patients. J Affect Disord 166:330–333. doi:10.1016/j.jad.2014.05.020

    Article  PubMed  CAS  Google Scholar 

  107. Kundakovic M, Gudsnuk K, Herbstman JB, Tang D, Perera FP, Champagne FA (2014) DNA methylation of BDNF as a biomarker of early-life adversity. Proc Natl Acad Sci USA. doi:10.1073/pnas.1408355111

    PubMed Central  PubMed  Google Scholar 

  108. Pena CJ, Bagot RC, Labonte B, Nestler EJ (2014) Epigenetic signaling in psychiatric disorders. J Mol Biol 426:3389–3412. doi:10.1016/j.jmb.2014.03.016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  109. Blaze J, Roth TL (2013) Exposure to caregiver maltreatment alters expression levels of epigenetic regulators in the medial prefrontal cortex. Int J Dev Neurosci 31:804–810. doi:10.1016/j.ijdevneu.2013.10.001

    Article  CAS  PubMed  Google Scholar 

  110. Levine A, Worrell TR, Zimnisky R, Schmauss C (2012) Early life stress triggers sustained changes in histone deacetylase expression and histone H4 modifications that alter responsiveness to adolescent antidepressant treatment. Neurobiol Dis 45:488–498. doi:10.1016/j.nbd.2011.09.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Xie L, Korkmaz KS, Braun K, Bock J (2013) Early life stress-induced histone acetylations correlate with activation of the synaptic plasticity genes Arc and Egr1 in the mouse hippocampus. J Neurochem 125:457–464. doi:10.1111/jnc.12210

    Article  CAS  PubMed  Google Scholar 

  112. Mueller BR, Bale TL (2008) Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 28:9055–9065. doi:10.1523/JNEUROSCI.1424-08.2008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  113. Non AL, Binder AM, Kubzansky LD, Michels KB (2014) Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety, or SSRI medication during pregnancy. Epigenetics 9:964–972. doi:10.4161/epi.28853

    Article  PubMed Central  PubMed  Google Scholar 

  114. Meaney MJ (2001) Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci 24:1161–1192. doi:10.1146/annurev.neuro.24.1.1161

    Article  CAS  PubMed  Google Scholar 

  115. Francis D, Diorio J, Liu D, Meaney MJ (1999) Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158

    Article  CAS  PubMed  Google Scholar 

  116. Yehuda R, Bell A, Bierer LM, Schmeidler J (2008) Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors. J Psychiatr Res 42:1104–1111. doi:10.1016/j.jpsychires.2008.01.002

    Article  PubMed Central  PubMed  Google Scholar 

  117. Franklin TB, Russig H, Weiss IC, Graff J, Linder N, Michalon A, Vizi S, Mansuy IM (2010) Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 68:408–415. doi:10.1016/j.biopsych.2010.05.036

    Article  PubMed  Google Scholar 

  118. Dietz DM, Laplant Q, Watts EL, Hodes GE, Russo SJ, Feng J, Oosting RS, Vialou V, Nestler EJ (2011) Paternal transmission of stress-induced pathologies. Biol Psychiatry 70:408–414. doi:10.1016/j.biopsych.2011.05.005

    Article  PubMed Central  PubMed  Google Scholar 

  119. Warner-Schmidt JL, Duman RS (2008) VEGF as a potential target for therapeutic intervention in depression. Curr Opin Pharmacol 8:14–19. doi:10.1016/j.coph.2007.10.013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  120. Greene J, Banasr M, Lee B, Warner-Schmidt J, Duman RS (2009) Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. Neuropsychopharmacology 34:2459–2468. doi:10.1038/npp.2009.68

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. de Jong IE, de Kloet ER (2004) Glucocorticoids and vulnerability to psychostimulant drugs: toward substrate and mechanism. Ann N Y Acad Sci 1018:192–198. doi:10.1196/annals.1296.022

    Article  PubMed  CAS  Google Scholar 

  122. Duman RS, Malberg J, Nakagawa S (2001) Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther 299:401–407

    CAS  PubMed  Google Scholar 

  123. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20:9104–9110. pii: 20/24/9104

  124. Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, Arango V (2009) Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34:2376–2389. doi:10.1038/npp.2009.75

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  125. Toni N, Laplagne DA, Zhao C, Lombardi G, Ribak CE, Gage FH, Schinder AF (2008) Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat Neurosci 11:901–907. doi:10.1038/nn.2156

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  126. Cameron HA, Gould E (1994) Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus. Neuroscience 61:203–209

    Article  CAS  PubMed  Google Scholar 

  127. Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17:879–886

    Article  PubMed  Google Scholar 

  128. Lee KJ, Kim SJ, Kim SW, Choi SH, Shin YC, Park SH, Moon BH, Cho E, Lee MS, Choi SH, Chun BG, Shin KH (2006) Chronic mild stress decreases survival, but not proliferation, of new-born cells in adult rat hippocampus. Exp Mol Med 38:44–54. doi:10.1038/emm.2006.6

    Article  CAS  PubMed  Google Scholar 

  129. Van Bokhoven P, Oomen CA, Hoogendijk WJ, Smit AB, Lucassen PJ, Spijker S (2011) Reduction in hippocampal neurogenesis after social defeat is long-lasting and responsive to late antidepressant treatment. Eur J Neurosci 33:1833–1840. doi:10.1111/j.1460-9568.2011.07668.x

    Article  PubMed  Google Scholar 

  130. Dranovsky A, Picchini AM, Moadel T, Sisti AC, Yamada A, Kimura S, Leonardo ED, Hen R (2011) Experience dictates stem cell fate in the adult hippocampus. Neuron 70:908–923. doi:10.1016/j.neuron.2011.05.022

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  131. Hanson ND, Owens MJ, Boss-Williams KA, Weiss JM, Nemeroff CB (2011) Several stressors fail to reduce adult hippocampal neurogenesis. Psychoneuroendocrinology 36:1520–1529. doi:10.1016/j.psyneuen.2011.04.006

    Article  PubMed Central  PubMed  Google Scholar 

  132. Miller BR, Hen R (2015) The current state of the neurogenic theory of depression and anxiety. Curr Opin Neurobiol 30:51–58. doi:10.1016/j.conb.2014.08.012

    Article  CAS  PubMed  Google Scholar 

  133. Sapolsky RM, Uno H, Rebert CS, Finch CE (1990) Hippocampal damage associated with prolonged glucocorticoid exposure in primates. J Neurosci 10:2897–2902

    CAS  PubMed  Google Scholar 

  134. Kunugi H, Hori H, Adachi N, Numakawa T (2010) Interface between hypothalamic–pituitary–adrenal axis and brain-derived neurotrophic factor in depression. Psychiatry Clin Neurosci 64:447–459. doi:10.1111/j.1440-1819.2010.02135.x

    Article  CAS  PubMed  Google Scholar 

  135. Benraiss A, Chmielnicki E, Lerner K, Roh D, Goldman SA (2001) Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain. J Neurosci 21:6718–6731

    CAS  PubMed  Google Scholar 

  136. Pencea V, Bingaman KD, Wiegand SJ, Luskin MB (2001) Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717

    CAS  PubMed  Google Scholar 

  137. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54:597–606

    Article  CAS  PubMed  Google Scholar 

  138. Murakami S, Imbe H, Morikawa Y, Kubo C, Senba E (2005) Chronic stress, as well as acute stress, reduces BDNF mRNA expression in the rat hippocampus but less robustly. Neurosci Res 53:129–139. doi:10.1016/j.neures.2005.06.008

    Article  CAS  PubMed  Google Scholar 

  139. Li Y, Luikart BW, Birnbaum S, Chen J, Kwon CH, Kernie SG, Bassel-Duby R, Parada LF (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412. doi:10.1016/j.neuron.2008.06.023

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  140. Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28:1562–1571. doi:10.1038/sj.npp.1300234

    Article  CAS  PubMed  Google Scholar 

  141. Chen H, Pandey GN, Dwivedi Y (2006) Hippocampal cell proliferation regulation by repeated stress and antidepressants. NeuroReport 17:863–867. doi:10.1097/01.wnr.0000221827.03222.70

    Article  PubMed  Google Scholar 

  142. Crupi R, Cambiaghi M, Spatz L, Hen R, Thorn M, Friedman E, Vita G, Battaglia F (2010) Reduced adult neurogenesis and altered emotional behaviors in autoimmune-prone B-cell activating factor transgenic mice. Biol Psychiatry 67:558–566. doi:10.1016/j.biopsych.2009.12.008

    Article  CAS  PubMed  Google Scholar 

  143. Anacker C, Zunszain PA, Cattaneo A, Carvalho LA, Garabedian MJ, Thuret S, Price J, Pariante CM (2011) Antidepressants increase human hippocampal neurogenesis by activating the glucocorticoid receptor. Mol Psychiatry 16:738–750. doi:10.1038/mp.2011.26

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  144. Holsboer F, Ising M (2010) Stress hormone regulation: biological role and translation into therapy. Annu Rev Psychol 61(81–109):C101–C111. doi:10.1146/annurev.psych.093008.100321

    Google Scholar 

  145. Mirescu C, Gould E (2006) Stress and adult neurogenesis. Hippocampus 16:233–238. doi:10.1002/hipo.20155

    Article  CAS  PubMed  Google Scholar 

  146. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476:458–461. doi:10.1038/nature10287

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  147. Hill AS, Sahay A, Hen R (2015) Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology. doi:10.1038/npp.2015.85

    Google Scholar 

  148. Lagace DC, Donovan MH, DeCarolis NA, Farnbauch LA, Malhotra S, Berton O, Nestler EJ, Krishnan V, Eisch AJ (2010) Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. Proc Natl Acad Sci USA 107:4436–4441. doi:10.1073/pnas.0910072107

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Lucassen PJ, Stumpel MW, Wang Q, Aronica E (2010) Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients. Neuropharmacology 58:940–949. doi:10.1016/j.neuropharm.2010.01.012

    Article  CAS  PubMed  Google Scholar 

  150. Deisseroth K, Singla S, Toda H, Monje M, Palmer TD, Malenka RC (2004) Excitation-neurogenesis coupling in adult neural stem/progenitor cells. Neuron 42:535–552

    Article  CAS  PubMed  Google Scholar 

  151. Wiskott L, Rasch MJ, Kempermann G (2006) A functional hypothesis for adult hippocampal neurogenesis: avoidance of catastrophic interference in the dentate gyrus. Hippocampus 16:329–343. doi:10.1002/hipo.20167

    Article  PubMed  Google Scholar 

  152. Pham K, McEwen BS, Ledoux JE, Nader K (2005) Fear learning transiently impairs hippocampal cell proliferation. Neuroscience 130:17–24. doi:10.1016/j.neuroscience.2004.09.015

    Article  CAS  PubMed  Google Scholar 

  153. Van der Borght K, Meerlo P, Luiten PG, Eggen BJ, Van der Zee EA (2005) Effects of active shock avoidance learning on hippocampal neurogenesis and plasma levels of corticosterone. Behav Brain Res 157:23–30. doi:10.1016/j.bbr.2004.06.004

    Article  PubMed  CAS  Google Scholar 

  154. Westenbroek C, Snijders TA, den Boer JA, Gerrits M, Fokkema DS, Ter Horst GJ (2005) Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses. Horm Behav 47:620–628. doi:10.1016/j.yhbeh.2005.01.004

    Article  CAS  PubMed  Google Scholar 

  155. Shors TJ, Mathew J, Sisti HM, Edgecomb C, Beckoff S, Dalla C (2007) Neurogenesis and helplessness are mediated by controllability in males but not in females. Biol Psychiatry 62:487–495. doi:10.1016/j.biopsych.2006.10.033

    Article  PubMed Central  PubMed  Google Scholar 

  156. Larson PS (2014) Deep brain stimulation for movement disorders. Neurotherapeutics 11:465–474. doi:10.1007/s13311-014-0274-1

    Article  PubMed Central  PubMed  Google Scholar 

  157. Sartorius A, Henn FA (2007) Deep brain stimulation of the lateral habenula in treatment resistant major depression. Med Hypotheses 69:1305–1308. doi:10.1016/j.mehy.2007.03.021

    Article  PubMed  Google Scholar 

  158. Schneider TM, Beynon C, Sartorius A, Unterberg AW, Kiening KL (2013) Deep brain stimulation of the lateral habenular complex in treatment-resistant depression: traps and pitfalls of trajectory choice. Neurosurgery 72:ons184–ons193. doi:10.1227/NEU.0b013e318277a5aa (discussion ons193)

    PubMed  Google Scholar 

  159. Berlim MT, McGirr A, Van den Eynde F, Fleck MP, Giacobbe P (2014) Effectiveness and acceptability of deep brain stimulation (DBS) of the subgenual cingulate cortex for treatment-resistant depression: a systematic review and exploratory meta-analysis. J Affect Disord 159:31–38. doi:10.1016/j.jad.2014.02.016

    Article  PubMed  Google Scholar 

  160. Bogod NM, Sinden M, Woo C, Defreitas VG, Torres IJ, Howard AK, Ilcewicz-Klimek MI, Honey CR, Yatham LN, Lam RW (2014) Long-term neuropsychological safety of subgenual cingulate gyrus deep brain stimulation for treatment-resistant depression. J Neuropsychiatry Clin Neurosci 26:126–133. doi:10.1176/appi.neuropsych.12110287

    Article  PubMed  Google Scholar 

  161. Dobrossy MD, Furlanetti LL, Coenen VA (2015) Electrical stimulation of the medial forebrain bundle in pre-clinical studies of psychiatric disorders. Neurosci Biobehav Rev 49:32–42. doi:10.1016/j.neubiorev.2014.11.018

    Article  PubMed  Google Scholar 

  162. Han MH, Friedman AK (2012) Virogenetic and optogenetic mechanisms to define potential therapeutic targets in psychiatric disorders. Neuropharmacology 62:89–100. doi:10.1016/j.neuropharm.2011.09.009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  163. Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW, Ferguson D, Tsai HC, Pomeranz L, Christoffel DJ, Nectow AR, Ekstrand M, Domingos A, Mazei-Robison MS, Mouzon E, Lobo MK, Neve RL, Friedman JM, Russo SJ, Deisseroth K, Nestler EJ, Han MH (2013) Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493:532–536. doi:10.1038/nature11713

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  164. Francis TC, Chandra R, Friend DM, Finkel E, Dayrit G, Miranda J, Brooks JM, Iniguez SD, O’Donnell P, Kravitz A, Lobo MK (2015) Nucleus accumbens medium spiny neuron subtypes mediate depression-related outcomes to social defeat stress. Biol Psychiatry 77:212–222. doi:10.1016/j.biopsych.2014.07.021

    Article  PubMed  Google Scholar 

  165. Francis TCCD, Lobo MK (2014) Optogenetics: illuminating the neural basis of rodent behavior. Open Access Anim Physiol 6:33–51

    Google Scholar 

  166. Lammel S, Lim BK, Malenka RC (2014) Reward and aversion in a heterogeneous midbrain dopamine system. Neuropharmacology 76 Pt B:351–359. doi:10.1016/j.neuropharm.2013.03.019

    Article  PubMed  CAS  Google Scholar 

  167. Tye KM, Prakash R, Kim SY, Fenno LE, Grosenick L, Zarabi H, Thompson KR, Gradinaru V, Ramakrishnan C, Deisseroth K (2011) Amygdala circuitry mediating reversible and bidirectional control of anxiety. Nature 471:358–362. doi:10.1038/nature09820

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  168. Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K (2013) Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493:537–541. doi:10.1038/nature11740

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  169. Koob GF (2008) A role for brain stress systems in addiction. Neuron 59:11–34. doi:10.1016/j.neuron.2008.06.012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  170. Wenzel JM, Rauscher NA, Cheer JF, Oleson EB (2015) A role for phasic dopamine release within the nucleus accumbens in encoding aversion: a review of the neurochemical literature. ACS Chem Neurosci 6:16–26. doi:10.1021/cn500255p

    Article  CAS  PubMed  Google Scholar 

  171. Cao JL, Covington HE 3rd, Friedman AK, Wilkinson MB, Walsh JJ, Cooper DC, Nestler EJ, Han MH (2010) Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action. J Neurosci 30:16453–16458. doi:10.1523/JNEUROSCI.3177-10.2010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  172. Friedman AK, Walsh JJ, Juarez B, Ku SM, Chaudhury D, Wang J, Li X, Dietz DM, Pan N, Vialou VF, Neve RL, Yue Z, Han MH (2014) Enhancing depression mechanisms in midbrain dopamine neurons achieves homeostatic resilience. Science 344:313–319. doi:10.1126/science.1249240

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  173. Anstrom KK, Miczek KA, Budygin EA (2009) Increased phasic dopamine signaling in the mesolimbic pathway during social defeat in rats. Neuroscience 161:3–12. doi:10.1016/j.neuroscience.2009.03.023

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  174. Razzoli M, Andreoli M, Michielin F, Quarta D, Sokal DM (2011) Increased phasic activity of VTA dopamine neurons in mice 3 weeks after repeated social defeat. Behav Brain Res 218:253–257. doi:10.1016/j.bbr.2010.11.050

    Article  CAS  PubMed  Google Scholar 

  175. Belujon P, Grace AA (2014) Restoring mood balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity. Biol Psychiatry 76:927–936. doi:10.1016/j.biopsych.2014.04.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Lammel S, Tye KM, Warden MR (2014) Progress in understanding mood disorders: optogenetic dissection of neural circuits. Genes Brain Behav 13:38–51. doi:10.1111/gbb.12049

    Article  CAS  PubMed  Google Scholar 

  177. Marton TF, Sohal VS (2015) Of mice, men, and microbial opsins: how optogenetics can help hone mouse models of mental illness. Biol Psychiatry. doi:10.1016/j.biopsych.2015.04.012

    PubMed  Google Scholar 

  178. Walsh JJ, Han MH (2014) The heterogeneity of ventral tegmental area neurons: projection functions in a mood-related context. Neuroscience 282C:101–108. doi:10.1016/j.neuroscience.2014.06.006

    Article  CAS  PubMed  Google Scholar 

  179. Valenti O, Gill KM, Grace AA (2012) Different stressors produce excitation or inhibition of mesolimbic dopamine neuron activity: response alteration by stress pre-exposure. Eur J Neurosci 35:1312–1321. doi:10.1111/j.1460-9568.2012.08038.x

    Article  PubMed Central  PubMed  Google Scholar 

  180. Brischoux F, Chakraborty S, Brierley DI, Ungless MA (2009) Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli. Proc Natl Acad Sci USA 106:4894–4899. doi:10.1073/pnas.0811507106

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  181. Lammel S, Ion DI, Roeper J, Malenka RC (2011) Projection-specific modulation of dopamine neuron synapses by aversive and rewarding stimuli. Neuron 70:855–862. doi:10.1016/j.neuron.2011.03.025

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  182. Lammel S, Lim BK, Ran C, Huang KW, Betley MJ, Tye KM, Deisseroth K, Malenka RC (2012) Input-specific control of reward and aversion in the ventral tegmental area. Nature 491:212–217. doi:10.1038/nature11527

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  183. Lecca S, Meye FJ, Mameli M (2014) The lateral habenula in addiction and depression: an anatomical, synaptic and behavioral overview. Eur J Neurosci 39:1170–1178. doi:10.1111/ejn.12480

    Article  PubMed  Google Scholar 

  184. Stamatakis AM, Stuber GD (2012) Activation of lateral habenula inputs to the ventral midbrain promotes behavioral avoidance. Nat Neurosci 15:1105–1107. doi:10.1038/nn.3145

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  185. Dipesh Chaudhury HZ, Juarez B, Friedman A, Ku S, Han M-H (2014) Lateral habenula projections to a subset of ventral tegmental area neurons rapidly encodes for susceptibility to social defeat stress. Soc Neurosci Abstr

  186. Shabel SJ, Proulx CD, Trias A, Murphy RT, Malinow R (2012) Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin. Neuron 74:475–481. doi:10.1016/j.neuron.2012.02.037

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  187. Ungless MA, Grace AA (2012) Are you or aren’t you? Challenges associated with physiologically identifying dopamine neurons. Trends Neurosci 35:422–430. doi:10.1016/j.tins.2012.02.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  188. Napier TC, Maslowski-Cobuzzi RJ (1994) Electrophysiological verification of the presence of D1 and D2 dopamine receptors within the ventral pallidum. Synapse 17:160–166. doi:10.1002/syn.890170304

    Article  CAS  PubMed  Google Scholar 

  189. Sesack SR, Grace AA (2010) Cortico-basal ganglia reward network: microcircuitry. Neuropsychopharmacology 35:27–47. doi:10.1038/npp.2009.93

    Article  PubMed Central  PubMed  Google Scholar 

  190. Chang CH, Grace AA (2014) Amygdala-ventral pallidum pathway decreases dopamine activity after chronic mild stress in rats. Biol Psychiatry 76:223–230. doi:10.1016/j.biopsych.2013.09.020

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  191. Michelsen KA, Prickaerts J, Steinbusch HW (2008) The dorsal raphe nucleus and serotonin: implications for neuroplasticity linked to major depression and Alzheimer’s disease. Prog Brain Res 172:233–264. doi:10.1016/S0079-6123(08)00912-6

    Article  CAS  PubMed  Google Scholar 

  192. Dolen G, Darvishzadeh A, Huang KW, Malenka RC (2013) Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501:179–184. doi:10.1038/nature12518

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  193. Soiza-Reilly M, Commons KG (2014) Unraveling the architecture of the dorsal raphe synaptic neuropil using high-resolution neuroanatomy. Front Neural Circuits 8:105. doi:10.3389/fncir.2014.00105

    Article  PubMed Central  PubMed  Google Scholar 

  194. Yang LM, Hu B, Xia YH, Zhang BL, Zhao H (2008) Lateral habenula lesions improve the behavioral response in depressed rats via increasing the serotonin level in dorsal raphe nucleus. Behav Brain Res 188:84–90. doi:10.1016/j.bbr.2007.10.022

    Article  PubMed  Google Scholar 

  195. Wang RY, Aghajanian GK (1977) Inhibiton of neurons in the amygdala by dorsal raphe stimulation: mediation through a direct serotonergic pathway. Brain Res 120:85–102

    Article  CAS  PubMed  Google Scholar 

  196. Ferraro G, Montalbano ME, Sardo P, La Grutta V (1996) Lateral habenular influence on dorsal raphe neurons. Brain Res Bull 41:47–52

    Article  CAS  PubMed  Google Scholar 

  197. Challis C, Beck SG, Berton O (2014) Optogenetic modulation of descending prefrontocortical inputs to the dorsal raphe bidirectionally bias socioaffective choices after social defeat. Front Behav Neurosci 8:43. doi:10.3389/fnbeh.2014.00043

    Article  PubMed Central  PubMed  Google Scholar 

  198. Challis C, Boulden J, Veerakumar A, Espallergues J, Vassoler FM, Pierce RC, Beck SG, Berton O (2013) Raphe GABAergic neurons mediate the acquisition of avoidance after social defeat. J Neurosci 33(13978–13988):13988a. doi:10.1523/JNEUROSCI.2383-13.2013

    Google Scholar 

  199. Curtis AL, Bello NT, Connolly KR, Valentino RJ (2002) Corticotropin-releasing factor neurones of the central nucleus of the amygdala mediate locus coeruleus activation by cardiovascular stress. J Neuroendocrinol 14:667–682

    Article  CAS  PubMed  Google Scholar 

  200. West CH, Ritchie JC, Boss-Williams KA, Weiss JM (2009) Antidepressant drugs with differing pharmacological actions decrease activity of locus coeruleus neurons. Int J Neuropsychopharmacol 12:627–641. doi:10.1017/S1461145708009474

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  201. Sara SJ (2009) The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci 10:211–223. doi:10.1038/nrn2573

    Article  CAS  PubMed  Google Scholar 

  202. Bruzos-Cidon C, Miguelez C, Rodriguez JJ, Gutierrez-Lanza R, Ugedo L, Torrecilla M (2014) Altered neuronal activity and differential sensitivity to acute antidepressants of locus coeruleus and dorsal raphe nucleus in Wistar Kyoto rats: a comparative study with Sprague Dawley and Wistar rats. Eur Neuropsychopharmacol 24:1112–1122. doi:10.1016/j.euroneuro.2014.02.007

    Article  CAS  PubMed  Google Scholar 

  203. Bruzos-Cidon C, Llamosas N, Ugedo L, Torrecilla M (2015) Dysfunctional inhibitory mechanisms in locus coeruleus neurons of the wistar kyoto rat. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyu122

    PubMed Central  Google Scholar 

  204. Covington HE 3rd, Lobo MK, Maze I, Vialou V, Hyman JM, Zaman S, LaPlant Q, Mouzon E, Ghose S, Tamminga CA, Neve RL, Deisseroth K, Nestler EJ (2010) Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex. J Neurosci 30:16082–16090. doi:10.1523/JNEUROSCI.1731-10.2010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  205. Thompson SM, Kallarackal AJ, Kvarta MD, Van Dyke AM, LeGates TA, Cai X (2015) An excitatory synapse hypothesis of depression. Trends Neurosci 38:279–294. doi:10.1016/j.tins.2015.03.003

    Article  CAS  PubMed  Google Scholar 

  206. Sears RM, Fink AE, Wigestrand MB, Farb CR, de Lecea L, Ledoux JE (2013) Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus. Proc Natl Acad Sci USA 110:20260–20265. doi:10.1073/pnas.1320325110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  207. Namburi P, Beyeler A, Yorozu S, Calhoon GG, Halbert SA, Wichmann R, Holden SS, Mertens KL, Anahtar M, Felix-Ortiz AC, Wickersham IR, Gray JM, Tye KM (2015) A circuit mechanism for differentiating positive and negative associations. Nature 520:675–678. doi:10.1038/nature14366

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  208. Johnson LR, Hou M, Prager EM, Ledoux JE (2011) Regulation of the fear network by mediators of stress: norepinephrine alters the balance between cortical and subcortical afferent excitation of the lateral amygdala. Front Behav Neurosci 5:23. doi:10.3389/fnbeh.2011.00023

    Article  PubMed Central  PubMed  Google Scholar 

  209. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184. doi:10.1146/annurev.neuro.23.1.155

    Article  CAS  PubMed  Google Scholar 

  210. Chang CH, Grace AA (2015) Dopaminergic modulation of lateral amygdala neuronal activity: differential D1 and D2 receptor effects on thalamic and cortical afferent inputs. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyv015

    Google Scholar 

  211. Belzung C, Willner P, Philippot P (2015) Depression: from psychopathology to pathophysiology. Curr Opin Neurobiol 30:24–30. doi:10.1016/j.conb.2014.08.013

    Article  CAS  PubMed  Google Scholar 

  212. Vialou V, Robison AJ, Laplant QC, Covington HE 3rd, Dietz DM, Ohnishi YN, Mouzon E, Rush AJ 3rd, Watts EL, Wallace DL, Iniguez SD, Ohnishi YH, Steiner MA, Warren BL, Krishnan V, Bolanos CA, Neve RL, Ghose S, Berton O, Tamminga CA, Nestler EJ (2010) DeltaFosB in brain reward circuits mediates resilience to stress and antidepressant responses. Nat Neurosci 13:745–752. doi:10.1038/nn.2551

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  213. Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, Temel Y (2015) Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms. Transl Psychiatry 5:e535. doi:10.1038/tp.2015.24

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  214. Nicola SM (2007) The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology 191:521–550. doi:10.1007/s00213-006-0510-4

    Article  CAS  PubMed  Google Scholar 

  215. Smith RJ, Lobo MK, Spencer S, Kalivas PW (2013) Cocaine-induced adaptations in D1 and D2 accumbens projection neurons (a dichotomy not necessarily synonymous with direct and indirect pathways). Curr Opin Neurobiol 23:546–552. doi:10.1016/j.conb.2013.01.026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  216. Albin RL, Young AB, Penney JB (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375

    Article  CAS  PubMed  Google Scholar 

  217. Maia TV, Frank MJ (2011) From reinforcement learning models to psychiatric and neurological disorders. Nat Neurosci 14:154–162. doi:10.1038/nn.2723

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  218. Kravitz AV, Kreitzer AC (2012) Striatal mechanisms underlying movement, reinforcement, and punishment. Physiology 27:167–177. doi:10.1152/physiol.00004.2012

    Article  PubMed  Google Scholar 

  219. Lenz JD, Lobo MK (2013) Optogenetic insights into striatal function and behavior. Behav Brain Res 255:44–54. doi:10.1016/j.bbr.2013.04.018

    Article  CAS  PubMed  Google Scholar 

  220. Carlezon WA Jr, Thomas MJ (2009) Biological substrates of reward and aversion: a nucleus accumbens activity hypothesis. Neuropharmacology 56(Suppl 1):122–132. doi:10.1016/j.neuropharm.2008.06.075

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  221. Lobo MK, Nestler EJ (2011) The striatal balancing act in drug addiction: distinct roles of direct and indirect pathway medium spiny neurons. Front Neuroanat 5:41. doi:10.3389/fnana.2011.00041

    Article  PubMed Central  PubMed  Google Scholar 

  222. Freeze BS, Kravitz AV, Hammack N, Berke JD, Kreitzer AC (2013) Control of basal ganglia output by direct and indirect pathway projection neurons. J Neurosci 33:18531–18539. doi:10.1523/JNEUROSCI.1278-13.2013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  223. Lobo MK, Zaman S, Damez-Werno DM, Koo JW, Bagot RC, DiNieri JA, Nugent A, Finkel E, Chaudhury D, Chandra R, Riberio E, Rabkin J, Mouzon E, Cachope R, Cheer JF, Han MH, Dietz DM, Self DW, Hurd YL, Vialou V, Nestler EJ (2013) DeltaFosB induction in striatal medium spiny neuron subtypes in response to chronic pharmacological, emotional, and optogenetic stimuli. J Neurosci 33:18381–18395. doi:10.1523/JNEUROSCI.1875-13.2013

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  224. Lim BK, Huang KW, Grueter BA, Rothwell PE, Malenka RC (2012) Anhedonia requires MC4R-mediated synaptic adaptations in nucleus accumbens. Nature 487:183–189. doi:10.1038/nature11160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  225. Bagot RC, Parise EM, Pena CJ, Zhang HX, Maze I, Chaudhury D, Persaud B, Cachope R, Bolanos-Guzman CA, Cheer J, Deisseroth K, Han MH, Nestler EJ (2015) Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression. Nature communications 6:7062. doi:10.1038/ncomms8062

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  226. McClung CA, Nestler EJ (2003) Regulation of gene expression and cocaine reward by CREB and DeltaFosB. Nat Neurosci 6:1208–1215. doi:10.1038/nn1143

    Article  CAS  PubMed  Google Scholar 

  227. Renthal W, Kumar A, Xiao G, Wilkinson M, Covington HE 3rd, Maze I, Sikder D, Robison AJ, LaPlant Q, Dietz DM, Russo SJ, Vialou V, Chakravarty S, Kodadek TJ, Stack A, Kabbaj M, Nestler EJ (2009) Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins. Neuron 62:335–348. doi:10.1016/j.neuron.2009.03.026

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  228. Bredt DS, Nicoll RA (2003) AMPA receptor trafficking at excitatory synapses. Neuron 40:361–379

    Article  CAS  PubMed  Google Scholar 

  229. Li DP, Byan HS, Pan HL (2012) Switch to glutamate receptor 2-lacking AMPA receptors increases neuronal excitability in hypothalamus and sympathetic drive in hypertension. J Neurosci 32:372–380. doi:10.1523/JNEUROSCI.3222-11.2012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  230. Grace AA, Floresco SB, Goto Y, Lodge DJ (2007) Regulation of firing of dopaminergic neurons and control of goal-directed behaviors. Trends Neurosci 30:220–227. doi:10.1016/j.tins.2007.03.003

    Article  CAS  PubMed  Google Scholar 

  231. Goto Y, Grace AA (2005) Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: disruption by cocaine sensitization. Neuron 47:255–266. doi:10.1016/j.neuron.2005.06.017

    Article  CAS  PubMed  Google Scholar 

  232. Goto Y, Grace AA (2005) Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neurosci 8:805–812. doi:10.1038/nn1471

    Article  CAS  PubMed  Google Scholar 

  233. O’Donnell P, Grace AA (1994) Tonic D2-mediated attenuation of cortical excitation in nucleus accumbens neurons recorded in vitro. Brain Res 634:105–112. pii: 0006-8993(94)90263-1

  234. West AR, Grace AA (2002) Opposite influences of endogenous dopamine D1 and D2 receptor activation on activity states and electrophysiological properties of striatal neurons: studies combining in vivo intracellular recordings and reverse microdialysis. J Neurosci 22:294–304. pii:22/1/294

  235. Kauer JA, Malenka RC (2007) Synaptic plasticity and addiction. Nat Rev Neurosci 8:844–858. doi:10.1038/nrn2234

    Article  CAS  PubMed  Google Scholar 

  236. Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10:647–658. doi:10.1038/nrn2699

    Article  CAS  PubMed  Google Scholar 

  237. Russo SJ, Dietz DM, Dumitriu D, Morrison JH, Malenka RC, Nestler EJ (2010) The addicted synapse: mechanisms of synaptic and structural plasticity in nucleus accumbens. Trends Neurosci 33:267–276. doi:10.1016/j.tins.2010.02.002

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  238. Luscher C, Malenka RC (2012) NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD). Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a005710

    PubMed Central  PubMed  Google Scholar 

  239. Radley JJ, Rocher AB, Miller M, Janssen WG, Liston C, Hof PR, McEwen BS, Morrison JH (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16:313–320. doi:10.1093/cercor/bhi104

    Article  PubMed  Google Scholar 

  240. Goldwater DS, Pavlides C, Hunter RG, Bloss EB, Hof PR, McEwen BS, Morrison JH (2009) Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 164:798–808. doi:10.1016/j.neuroscience.2009.08.053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  241. Shansky RM, Hamo C, Hof PR, McEwen BS, Morrison JH (2009) Stress-induced dendritic remodeling in the prefrontal cortex is circuit specific. Cereb Cortex 19:2479–2484. doi:10.1093/cercor/bhp003

    Article  PubMed Central  PubMed  Google Scholar 

  242. Chakravarthy S, Saiepour MH, Bence M, Perry S, Hartman R, Couey JJ, Mansvelder HD, Levelt CN (2006) Postsynaptic TrkB signaling has distinct roles in spine maintenance in adult visual cortex and hippocampus. Proc Natl Acad Sci USA 103:1071–1076. doi:10.1073/pnas.0506305103

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  243. Russo SJ, Wilkinson MB, Mazei-Robison MS, Dietz DM, Maze I, Krishnan V, Renthal W, Graham A, Birnbaum SG, Green TA, Robison B, Lesselyong A, Perrotti LI, Bolanos CA, Kumar A, Clark MS, Neumaier JF, Neve RL, Bhakar AL, Barker PA, Nestler EJ (2009) Nuclear factor kappa B signaling regulates neuronal morphology and cocaine reward. J Neurosci 29:3529–3537. doi:10.1523/JNEUROSCI.6173-08.2009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  244. Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59:1151–1159. doi:10.1016/j.biopsych.2005.09.018

    Article  CAS  PubMed  Google Scholar 

  245. Wanat MJ, Hopf FW, Stuber GD, Phillips PE, Bonci A (2008) Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih. J Physiol 586:2157–2170. doi:10.1113/jphysiol.2007.150078

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  246. Neuhoff H, Neu A, Liss B, Roeper J (2002) I(h) channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain. J Neurosci 22:1290–1302

    CAS  PubMed  Google Scholar 

  247. Zhang J, Shapiro MS (2012) Activity-dependent transcriptional regulation of M-Type (Kv7) K(+) channels by AKAP79/150-mediated NFAT actions. Neuron 76:1133–1146. doi:10.1016/j.neuron.2012.10.019

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  248. Destexhe A, Marder E (2004) Plasticity in single neuron and circuit computations. Nature 431:789–795. doi:10.1038/nature03011

    Article  CAS  PubMed  Google Scholar 

  249. Whalley K (2013) Synaptic plasticity: balancing firing rates in vivo. Nat Rev Neurosci 14:820–821. doi:10.1038/nrn3637

    Article  PubMed  CAS  Google Scholar 

  250. Dickman DK, Davis GW (2009) The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis. Science 326:1127–1130. doi:10.1126/science.1179685

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  251. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65:732–741. doi:10.1016/j.biopsych.2008.11.029

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  252. Hashimoto K (2015) Inflammatory biomarkers as differential predictors of antidepressant response. Int J Mol Sci 16:7796–7801. doi:10.3390/ijms16047796

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  253. Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K (2011) Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry 16:751–762. doi:10.1038/mp.2010.52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  254. Himmerich H, Fischer J, Bauer K, Kirkby KC, Sack U, Krugel U (2013) Stress-induced cytokine changes in rats. Eur Cytokine Netw 24:97–103. doi:10.1684/ecn.2013.0338

    CAS  PubMed  Google Scholar 

  255. O’Connor MF, Irwin MR, Wellisch DK (2009) When grief heats up: pro-inflammatory cytokines predict regional brain activation. Neuroimage 47:891–896. doi:10.1016/j.neuroimage.2009.05.049

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  256. Kaster MP, Gadotti VM, Calixto JB, Santos AR, Rodrigues AL (2012) Depressive-like behavior induced by tumor necrosis factor-alpha in mice. Neuropharmacology 62:419–426. doi:10.1016/j.neuropharm.2011.08.018

    Article  CAS  PubMed  Google Scholar 

  257. Hetman M, Gozdz A (2004) Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. Eur J Biochem 271:2050–2055. doi:10.1111/j.1432-1033.2004.04133.x

    Article  CAS  PubMed  Google Scholar 

  258. Subramaniam S, Unsicker K (2010) ERK and cell death: ERK1/2 in neuronal death. FEBS J 277:22–29. doi:10.1111/j.1742-4658.2009.07367.x

    Article  CAS  PubMed  Google Scholar 

  259. Gantke T, Sriskantharajah S, Sadowski M, Ley SC (2012) IkappaB kinase regulation of the TPL-2/ERK MAPK pathway. Immunol Rev 246:168–182. doi:10.1111/j.1600-065X.2012.01104.x

    Article  PubMed  CAS  Google Scholar 

  260. Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L, Manji HK, Chen G (2003) The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 23:7311–7316

    CAS  PubMed  Google Scholar 

  261. Dwivedi Y, Rizavi HS, Conley RR, Pandey GN (2006) ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf. Mol Psychiatry 11:86–98. doi:10.1038/sj.mp.4001744

    Article  CAS  PubMed  Google Scholar 

  262. Gourley SL, Wu FJ, Kiraly DD, Ploski JE, Kedves AT, Duman RS, Taylor JR (2008) Regionally specific regulation of ERK MAP kinase in a model of antidepressant-sensitive chronic depression. Biol Psychiatry 63:353–359. doi:10.1016/j.biopsych.2007.07.016

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  263. Iniguez SD, Vialou V, Warren BL, Cao JL, Alcantara LF, Davis LC, Manojlovic Z, Neve RL, Russo SJ, Han MH, Nestler EJ, Bolanos-Guzman CA (2010) Extracellular signal-regulated kinase-2 within the ventral tegmental area regulates responses to stress. J Neurosci 30:7652–7663. doi:10.1523/JNEUROSCI.0951-10.2010

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  264. Kaminska B (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy–from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 1754:253–262. doi:10.1016/j.bbapap.2005.08.017

    Article  CAS  PubMed  Google Scholar 

  265. Hodes GE, Pfau ML, Leboeuf M, Golden SA, Christoffel DJ, Bregman D, Rebusi N, Heshmati M, Aleyasin H, Warren BL, Lebonte B, Horn S, Lapidus KA, Stelzhammer V, Wong EH, Bahn S, Krishnan V, Bolanos-Guzman CA, Murrough JW, Merad M, Russo SJ (2014) Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress. Proc Natl Acad Sci USA 111:16136–16141. doi:10.1073/pnas.1415191111

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  266. Perez-Caballero L, Perez-Egea R, Romero-Grimaldi C, Puigdemont D, Molet J, Caso JR, Mico JA, Perez V, Leza JC, Berrocoso E (2014) Early responses to deep brain stimulation in depression are modulated by anti-inflammatory drugs. Mol Psychiatry 19:607–614. doi:10.1038/mp.2013.63

    Article  CAS  PubMed  Google Scholar 

  267. McClung CA (2007) Circadian genes, rhythms and the biology of mood disorders. Pharmacol Ther 114:222–232. doi:10.1016/j.pharmthera.2007.02.003

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  268. Wirz-Justice A (2006) Biological rhythm disturbances in mood disorders. Int Clin Psychopharmacol 21(Suppl 1):S11–S15. doi:10.1097/01.yic.0000195660.37267.cf

    Article  PubMed  Google Scholar 

  269. Boivin DB, Czeisler CA, Dijk DJ, Duffy JF, Folkard S, Minors DS, Totterdell P, Waterhouse JM (1997) Complex interaction of the sleep-wake cycle and circadian phase modulates mood in healthy subjects. Arch Gen Psychiatry 54:145–152

    Article  CAS  PubMed  Google Scholar 

  270. Birchler-Pedross A, Schroder CM, Munch M, Knoblauch V, Blatter K, Schnitzler-Sack C, Wirz-Justice A, Cajochen C (2009) Subjective well-being is modulated by circadian phase, sleep pressure, age, and gender. J Biol Rhythms 24:232–242. doi:10.1177/0748730409335546

    Article  PubMed  Google Scholar 

  271. Sidor MM, McClung CA (2014) Timing matters: using optogenetics to chronically manipulate neural circuitry and rhythms. Front Behav Neurosci 8:41. doi:10.3389/fnbeh.2014.00041

    Article  PubMed Central  PubMed  Google Scholar 

  272. Ehlers CL, Kupfer DJ (1987) Hypothalamic peptide modulation of EEG sleep in depression: a further application of the S-process hypothesis. Biol Psychiatry 22:513–517

    Article  CAS  PubMed  Google Scholar 

  273. Bunney BG, Bunney WE (2012) Rapid-acting antidepressant strategies: mechanisms of action. Int J Neuropsychopharmacol 15:695–713. doi:10.1017/S1461145711000927

    Article  CAS  PubMed  Google Scholar 

  274. Benedetti F, Colombo C, Serretti A, Lorenzi C, Pontiggia A, Barbini B, Smeraldi E (2003) Antidepressant effects of light therapy combined with sleep deprivation are influenced by a functional polymorphism within the promoter of the serotonin transporter gene. Biol Psychiatry 54:687–692

    Article  CAS  PubMed  Google Scholar 

  275. Wirz-Justice A, Van den Hoofdakker RH (1999) Sleep deprivation in depression: what do we know, where do we go? Biol Psychiatry 46:445–453. pii: S0006-3223(99)00125-0

  276. Wu JC, Bunney WE (1990) The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry 147:14–21

    Article  CAS  PubMed  Google Scholar 

  277. Bunney BG, Bunney WE (2013) Mechanisms of rapid antidepressant effects of sleep deprivation therapy: clock genes and circadian rhythms. Biol Psychiatry 73:1164–1171. doi:10.1016/j.biopsych.2012.07.020

    Article  CAS  PubMed  Google Scholar 

  278. Bunney BG, Li JZ, Walsh DM, Stein R, Vawter MP, Cartagena P, Barchas JD, Schatzberg AF, Myers RM, Watson SJ, Akil H, Bunney WE (2015) Circadian dysregulation of clock genes: clues to rapid treatments in major depressive disorder. Mol Psychiatry 20:48–55. doi:10.1038/mp.2014.138

    Article  CAS  PubMed  Google Scholar 

  279. Sequeira A, Morgan L, Walsh DM, Cartagena PM, Choudary P, Li J, Schatzberg AF, Watson SJ, Akil H, Myers RM, Jones EG, Bunney WE, Vawter MP (2012) Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide. PLoS ONE 7:e35367. doi:10.1371/journal.pone.0035367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  280. Li JZ, Bunney BG, Meng F, Hagenauer MH, Walsh DM, Vawter MP, Evans SJ, Choudary PV, Cartagena P, Barchas JD, Schatzberg AF, Jones EG, Myers RM, Watson SJ Jr, Akil H, Bunney WE (2013) Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci USA 110:9950–9955. doi:10.1073/pnas.1305814110

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  281. Kinn AM, Gronli J, Fiske E, Kuipers S, Ursin R, Murison R, Portas CM (2008) A double exposure to social defeat induces sub-chronic effects on sleep and open field behaviour in rats. Physiol Behav 95:553–561. doi:10.1016/j.physbeh.2008.07.031

    Article  CAS  PubMed  Google Scholar 

  282. Spencer S, Falcon E, Kumar J, Krishnan V, Mukherjee S, Birnbaum SG, McClung CA (2013) Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety-related behavior. Eur J Neurosci 37:242–250. doi:10.1111/ejn.12010

    Article  PubMed Central  PubMed  Google Scholar 

  283. Slattery DA, Uschold N, Magoni M, Bar J, Popoli M, Neumann ID, Reber SO (2012) Behavioural consequences of two chronic psychosocial stress paradigms: anxiety without depression. Psychoneuroendocrinology 37:702–714. doi:10.1016/j.psyneuen.2011.09.002

    Article  PubMed  Google Scholar 

  284. Meerlo P, Turek FW (2001) Effects of social stimuli on sleep in mice: non-rapid-eye-movement (NREM) sleep is promoted by aggressive interaction but not by sexual interaction. Brain Res 907:84–92

    Article  CAS  PubMed  Google Scholar 

  285. Meerlo P, Overkamp GJ, Benning MA, Koolhaas JM, Van den Hoofdakker RH (1996) Long-term changes in open field behaviour following a single social defeat in rats can be reversed by sleep deprivation. Physiol Behav 60:115–119. pii: 0031938495022716

  286. Lavebratt C, Sjoholm LK, Soronen P, Paunio T, Vawter MP, Bunney WE, Adolfsson R, Forsell Y, Wu JC, Kelsoe JR, Partonen T, Schalling M (2010) CRY2 is associated with depression. PLoS ONE 5:e9407. doi:10.1371/journal.pone.0009407

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  287. Kavcic P, Rojc B, Dolenc-Groselj L, Claustrat B, Fujs K, Poljak M (2011) The impact of sleep deprivation and nighttime light exposure on clock gene expression in humans. Croat Med J 52:594–603

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  288. Wisor JP, O’Hara BF, Terao A, Selby CP, Kilduff TS, Sancar A, Edgar DM, Franken P (2002) A role for cryptochromes in sleep regulation. BMC Neurosci 3:20

    Article  PubMed Central  PubMed  Google Scholar 

  289. Wisor JP, Pasumarthi RK, Gerashchenko D, Thompson CL, Pathak S, Sancar A, Franken P, Lein ES, Kilduff TS (2008) Sleep deprivation effects on circadian clock gene expression in the cerebral cortex parallel electroencephalographic differences among mouse strains. J Neurosci 28:7193–7201. doi:10.1523/JNEUROSCI.1150-08.2008

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  290. Mongrain V, La Spada F, Curie T, Franken P (2011) Sleep loss reduces the DNA-binding of BMAL1, CLOCK, and NPAS2 to specific clock genes in the mouse cerebral cortex. PLoS One 6:e26622. doi:10.1371/journal.pone.0026622

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  291. Bellet MM, Vawter MP, Bunney BG, Bunney WE, Sassone-Corsi P (2011) Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression. PLoS One 6:e23982. doi:10.1371/journal.pone.0023982

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  292. Gottschlich MM, Mayes T, Khoury J, McCall J, Simakajornboon N, Kagan RJ (2011) The effect of ketamine administration on nocturnal sleep architecture. J Burn Care Res 32:535–540. doi:10.1097/BCR.0b013e31822ac7d1

    Article  PubMed  Google Scholar 

  293. Mukherjee S, Coque L, Cao JL, Kumar J, Chakravarty S, Asaithamby A, Graham A, Gordon E, Enwright JF 3rd, DiLeone RJ, Birnbaum SG, Cooper DC, McClung CA (2010) Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol Psychiatry 68:503–511. doi:10.1016/j.biopsych.2010.04.031

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  294. Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JF 3rd, Jacobsen JP, Kumar S, Remillard EM, Caron MG, Deisseroth K, McClung CA (2015) Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice. Mol Psychiatry. doi:10.1038/mp.2014.167

    Google Scholar 

  295. Hampp G, Ripperger JA, Houben T, Schmutz I, Blex C, Perreau-Lenz S, Brunk I, Spanagel R, Ahnert-Hilger G, Meijer JH, Albrecht U (2008) Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 18:678–683. doi:10.1016/j.cub.2008.04.012

    Article  CAS  PubMed  Google Scholar 

  296. Kondratova AA, Dubrovsky YV, Antoch MP, Kondratov RV (2010) Circadian clock proteins control adaptation to novel environment and memory formation. Aging 2:285–297

    CAS  PubMed  Google Scholar 

  297. De Bundel D, Gangarossa G, Biever A, Bonnefont X, Valjent E (2013) Cognitive dysfunction, elevated anxiety, and reduced cocaine response in circadian clock-deficient cryptochrome knockout mice. Front Behav Neurosci 7:152. doi:10.3389/fnbeh.2013.00152

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  298. Chung S, Lee EJ, Yun S, Choe HK, Park SB, Son HJ, Kim KS, Dluzen DE, Lee I, Hwang O, Son GH, Kim K (2014) Impact of circadian nuclear receptor REV-ERBalpha on midbrain dopamine production and mood regulation. Cell 157:858–868. doi:10.1016/j.cell.2014.03.039

    Article  CAS  PubMed  Google Scholar 

  299. Panksepp JB, Wong JC, Kennedy BC, Lahvis GP (2008) Differential entrainment of a social rhythm in adolescent mice. Behav Brain Res 195:239–245. doi:10.1016/j.bbr.2008.09.010

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Institute of Mental Health (MH092306: M.H.H.), Johnson & Johnson/International Mental Health Research Organization (M.H.H.), NARSAD Independent Investigator Award (M.H.H.), and NARSAD Young Investigator Award (D.C.).

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  1. Division of Science, Experimental Research Building, Office 106, New York University Abu Dhabi (NYUAD), Saadiyat Island Campus, P.O. Box 129188, Abu Dhabi, United Arab Emirates

    Dipesh Chaudhury & He Liu

  2. Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Ming-Hu Han

  3. Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Ming-Hu Han

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  1. Dipesh Chaudhury
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  2. He Liu
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Correspondence to Dipesh Chaudhury or Ming-Hu Han.

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Chaudhury, D., Liu, H. & Han, MH. Neuronal correlates of depression. Cell. Mol. Life Sci. 72, 4825–4848 (2015). https://doi.org/10.1007/s00018-015-2044-6

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