Adult Hippocampal Neurogenesis, Fear Generalization, and Stress

Neuropsychopharmacology

Volumn 41, Issue 1, 2016, Pages 24-44

  Besnard, Antoine ^a   Sahay, Amar ^a,b,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b HARVARD STEM CELL INSTITUTE   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACCURACY; BRAIN CORTEX; CONFLICT; DENTATE GYRUS; FEAR; GRANULE CELL; HIPPOCAMPAL CA3 REGION; HUMAN; LONG TERM MEMORY; MEMORY; MOSSY FIBER; NEGATIVE FEEDBACK; NERVOUS SYSTEM DEVELOPMENT; NEUROBIOLOGY; NONHUMAN; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; REVIEW; STRESS; THREAT; ADULT; ANIMAL; HIPPOCAMPUS; MENTAL STRESS; METABOLISM; NERVE CELL NETWORK; PATHOLOGY; PHYSIOLOGY; PSYCHOLOGY;

ADULT; ANIMALS; FEAR; HIPPOCAMPUS; HUMANS; NERVE NET; NEUROGENESIS; STRESS DISORDERS, POST-TRAUMATIC; STRESS, PSYCHOLOGICAL;

EID: 84949625589     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2015.167     Document Type: Review

References (285)

1. Acheson DT, Gresack JE, Risbrough VB (2012). Hippocampal dysfunction effects on context memory: possible etiology for posttraumatic stress disorder. Neuropharmacology 62: 674-685.
2. Acsady L, Kali S (2007). Models, structure, function: the transformation of cortical signals in the dentate gyrus. Prog Brain Res 163: 577-599.
3. Acsady L, Kamondi A, Sik A, Freund T, Buzsaki G (1998). GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J Neurosc 18: 3386-3403.
4. Afifi TO, Asmundson GJ, Taylor S, Jang KL (2010). The role of genes and environment on trauma exposure and posttraumatic stress disorder symptoms: a review of twin studies. Clin Psychol Rev 30: 101-112.
5. Aimone JB, Deng W, Gage FH (2010). Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci 14: 325-337.
6. Aimone JB, Deng W, Gage FH (2011). Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron 70: 589-596.
7. Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014). Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94: 991-1026.
8. Aimone JB, Wiles J, Gage FH (2006). Potential role for adult neurogenesis in the encoding of time in new memories. Nat Neurosci 9: 723-727.
9. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro A, Hsiang HL et al (2014). Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344: 598-602.
10. Altman J, Das GD (1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124: 319-335. First report suggesting the existence of neurogenesis in the hippocampus of adult mammals (rats) by labeling adult generated cells with Tritiated thymidine.
11. Alvarez RP, Chen G, Bodurka J, Kaplan R, Grillon C (2011). Phasic and sustained fear in humans elicits distinct patterns of brain activity. Neuroimage 55: 389-400.
12. Andrews-Zwilling Y, Gillespie AK, Kravitz AV, Nelson AB, Devidze N, Lo I et al (2012). Hilar GABAergic interneuron activity controls spatial learning and memory retrieval. PLoS One 7: e40555.
13. Anthony TE, Dee N, Bernard A, Lerchner W, Heintz N, Anderson DJ (2014). Control of stress-induced persistent anxiety by an extra-amygdala septohypothalamic circuit. Cell 156: 522-536.
14. Antoniadis EA, McDonald RJ (2000). Amygdala, hippocampus and discriminative fear conditioning to context. Behav Brain Res 108: 1-19.
15. Arruda-Carvalho M, Sakaguchi M, Akers KG, Josselyn SA, Frankland PW (2011). Posttraining ablation of adult-generated neurons degrades previously acquired memories. J Neurosci 31: 15113-15127.
16. Bakker A, Kirwan CB, Miller M, Stark CE (2008). Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 319: 1640-1642. First demonstration for pattern separation-like functions in the human dentate gyrus-CA3 circuit using fMRI.
17. Bannerman DM, Sprengel R, Sanderson DJ, McHugh SB, Rawlins JN, Monyer H et al (2014). Hippocampal synaptic plasticity, spatial memory and anxiety. Nat Rev Neurosci 15: 181-192. Discussion on the roles of the hippocampus in conflict resolution and threat appraisal.
18. Becker S, Wojtowicz JM (2007). A model of hippocampal neurogenesis in memory and mood disorders. Trends Cogn Sci 11: 70-76.
19. Bergami M, Masserdotti G, Temprana SG, Motori E, Eriksson TM, Gobel J et al (2015). A critical period for experience-dependent remodeling of adult-born neuron connectivity. Neuron 85: 710-717.
20. Besnard A, Caboche J, Laroche S (2012). Reconsolidation of memory: a decade of debate. Prog Neurobiol 99: 61-80.
21. Biedenkapp JC, Rudy JW (2007). Context preexposure prevents forgetting of a contextual fear memory: implication for regional changes in brain activation patterns associated with recent and remote memory tests. Learn Mem 14: 200-203. Remote fear memories lose their context specificity over time.
22. Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J et al (2009). Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34: 2376-2389.
23. Bragin A, Jando G, Nadasdy Z, van Landeghem M, Buzsaki G (1995). Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat. J Neurophysiol 73: 1691-1705.
24. Burghardt NS, Park EH, Hen R, Fenton AA (2012). Adult-born hippocampal neurons promote cognitive flexibility in mice. Hippocampus 22: 1795-1808. The authors used a genetic approach to show that adult-born dentate granule neurons are necessary for cognitive flexibility in an active avoidance task and for maintaining sparseness of activity in the dentate gyrus.
25. Cameron HA, Glover LR (2015). Adult neurogenesis: beyond learning and memory. Annu Rev Psychol 66: 53-81.
26. Cameron HA, Woolley CS, McEwen BS, Gould E (1993). Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience 56: 337-344.
27. Campeau S, Watson SJ Jr (2000). Connections of some auditory-responsive posterior thalamic nuclei putatively involved in activation of the hypothalamopituitary-adrenocortical axis in response to audiogenic stress in rats: an anterograde and retrograde tract tracing study combined with Fos expression. J Comp Neurol 423: 474-491.
28. Carr MF, Jadhav SP, Frank LM (2011). Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat Neurosci 14: 147-153.
29. Catani C, Jacob N, Schauer E, Kohila M, Neuner F (2008). Family violence, war, and natural disasters: a study of the effect of extreme stress on children's mental health in Sri Lanka. BMC Psychiatry 8: 33.
30. Cerasti E, Treves A (2010). How informative are spatial CA3 representations established by the dentate gyrus? PLoS Comput Biol 6: e1000759.
31. Chaudhury D, Walsh JJ, Friedman AK, Juarez B, Ku SM, Koo JW et al (2013). Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493: 532-536.
32. Chawla MK, Guzowski JF, Ramirez-Amaya V, Lipa P, Hoffman KL, Marriott LK et al (2005). Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15: 579-586.
33. Chen F, Tillberg PW, Boyden ES (2015a). Optical imaging. Expansion microscopy. Science 347: 543-548.
34. Chen JL, Andermann ML, Keck T, Xu NL, Ziv Y (2013). Imaging neuronal populations in behaving rodents: paradigms for studying neural circuits underlying behavior in the mammalian cortex. J Neurosci 33: 17631-17640.
35. Chen Y, Lin YC, Kuo TW, Knight ZA (2015b). Sensory detection of food rapidly modulates arcuate feeding circuits. Cell 160: 829-841.
36. Christian KM, Song H, Ming GL (2014). Functions and dysfunctions of adult hippocampal neurogenesis. Annu Rev Neurosci 37: 243-262.
37. Chung K, Wallace J, Kim SY, Kalyanasundaram S, Andalman AS, Davidson TJ et al (2013). Structural and molecular interrogation of intact biological systems. Nature 497: 332-337. Tissue-clearing technique that renders intact tissue transparent while preserving its structural integrity.
38. Chuong AS, Miri ML, Busskamp V, Matthews GA, Acker LC, Sørensen AT et al (2014). Noninvasive optical inhibition with a red-shifted microbial rhodopsin. Nat Neurosci 17: 1123-1129. Bioengineering of far-red light-sensitive opsins that allow silencing of deep brain neuron by noninvasive transcranial light application.
39. Clelland CD, Choi M, Romberg C, Clemenson GD Jr, Fragniere A, Tyers P et al (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science 325: 210-213. Study showing that adult hippocampal neurogenesis is necessary for behavioral discrimination of overlapping spatial cues.
40. Colgin LL, Moser EI, Moser MB (2008). Understanding memory through hippocampal remapping. Trends Neurosci 31: 469-477.
41. Cornelis MC, Nugent NR, Amstadter AB, Koenen KC (2010). Genetics of posttraumatic stress disorder: review and recommendations for genome-wide association studies. Curr Psychiatry Rep 12 313-326.
42. Cowansage KK, Shuman T, Dillingham BC, Chang A, Golshani P, Mayford M (2014). Direct reactivation of a coherent neocortical memory of context. Neuron 84: 432-441.
43. Creer DJ, Romberg C, Saksida LM, van Praag H, Bussey TJ (2010). Running enhances spatial pattern separation in mice. Proc Natl Acad Sci USA 107: 2367-2372.
44. Czerniawski J, Guzowski JF (2014). Acute neuroinflammation impairs context discrimination memory and disrupts pattern separation processes in hippocampus. J Neurosci 34: 12470-12480.
45. de Lavilleon G, Lacroix MM, Rondi-Reig L, Benchenane K (2015). Explicit memory creation during sleep demonstrates a causal role of place cells in navigation. Nat Neurosci 18: 493-495.
46. Deisseroth K (2014). Circuit dynamics of adaptive and maladaptive behaviour. Nature 505: 309-317.
47. Deng W, Aimone JB, Gage FH (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11: 339-350.
48. Deng W, Mayford M, Gage FH (2013). Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice. Elife 2: e00312 Discrimination of similar contexts is associated with global remapping in the DG.
49. Denny CA, Kheirbek MA, Alba EL, Tanaka KF, Brachman RA, Laughman KB et al (2014). Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83: 189-201. Time-dependent fear generalization is associated with decreased global remapping in DG.
50. Dery N, Pilgrim M, Gibala M, Gillen J, Wojtowicz JM, Macqueen G et al (2013). Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression. Front Neurosci 7: 66.
51. Deuker L, Doeller CF, Fell J, Axmacher N (2014). Human neuroimaging studies on the hippocampal CA3 region-integrating evidence for pattern separation and completion. Front Cell Neurosci 8: 64.
52. Dias BG, Maddox SA, Klengel T, Ressler KJ (2015). Epigenetic mechanisms underlying learning and the inheritance of learned behaviors. Trends Neurosci 38: 96-107.
53. Dieni CV, Nietz AK, Panichi R, Wadiche JI, Overstreet-Wadiche L (2013). Distinct determinants of sparse activation during granule cell maturation. J Neurosci 33: 19131-19142.
54. Drew LJ, Fusi S, Hen R (2013). Adult neurogenesis in the mammalian hippocampus: why the dentate gyrus? Learn Mem 20: 710-729.
55. Dudai Y (2012). The restless engram: consolidations never end. Annu Rev Neurosci 35: 227-247.
56. Eriksson PS, Perfilieva E, Bjork-Eriksson T, Alborn AM, Nordborg C, Peterson DA et al (1998). Neurogenesis in the adult human hippocampus. Nat Med 4: 1313-1317. First demonstration of adult hippocampal neurogenesis in the human brain by bromodeoxyuridine (BrdU) labeling.
57. Ernst A, Frisen J (2015). Adult neurogenesis in humans-common and unique traits in mammals. PLoS Biol 13: e1002045.
58. Esposito MS, Piatti VC, Laplagne DA, Morgenstern NA, Ferrari CC, Pitossi FJ et al (2005). Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J Neurosci 25: 10074-10086.
59. Felix-Ortiz AC, Beyeler A, Seo C, Leppla CA, Wildes CP, Tye KM (2013). BLA to vHPC inputs modulate anxiety-related behaviors. Neuron 79: 658-664.
60. Foa EB, Zinbarg R, Rothbaum BO (1992). Uncontrollability and unpredictability in post-traumatic stress disorder: an animal model. Psychol Bull 112: 218-238.
61. Frankland PW, Bontempi B (2005). The organization of recent and remote memories. Nat Rev Neuroscience 6: 119-130.
62. Frankland PW, Cestari V, Filipkowski RK, McDonald RJ, Silva AJ (1998). The dorsal hippocampus is essential for context discrimination but not for contextual conditioning. Behav Neurosci 112: 863-874. Dorsal hippocampal lesions prevents contextual fear discrimination learning in mice.
63. Frankland PW, Josselyn SA (2015). Memory allocation. Neuropsychopharmacology 40: 243.
64. Frankland PW, Kohler S, Josselyn SA (2013). Hippocampal neurogenesis and forgetting. Trends Neurosci 36: 497-503.
65. Freund J, Brandmaier AM, Lewejohann L, Kirste I, Kritzler M, Kruger A et al (2013). Emergence of individuality in genetically identical mice. Science 340: 756-759.
66. Freund TF, Buzsaki G (1996). Interneurons of the hippocampus. Hippocampus 6: 347-470.
67. Fujii T, Saito DN, Yanaka HT, Kosaka H, Okazawa H (2014). Depressive mood modulates the anterior lateral CA1 and DG/CA3 during a pattern separation task in cognitively intact individuals: a functional MRI study. Hippocampus 24: 214-224.
68. Garcia A, Steiner B, Kronenberg G, Bick-Sander A, Kempermann G (2004). Agedependent expression of glucocorticoid-and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Aging Cell 3: 363-371.
69. Garcia I, Huang L, Ung K, Arenkiel BR (2012b). Tracing synaptic connectivity onto embryonic stem cell-derived neurons. Stem Cells 30: 2140-2151.
70. Garcia I, Kim C, Arenkiel BR (2012a). Genetic strategies to investigate neuronal circuit properties using stem cell-derived neurons. Front Cell Neurosci 6: 59.
71. Garthe A, Behr J, Kempermann G (2009). Adult-generated hippocampal neurons allow the flexible use of spatially precise learning strategies. PLoS One 4: e5464 Study used a chemical agent to block adult hippocampal neurogenesis and found a role for adult-born neurons in modulating proactive interference and cognitive flexibility.
72. Garthe A, Kempermann G (2013). An old test for new neurons: refining the Morris water maze to study the functional relevance of adult hippocampal neurogenesis. Front Neurosci 7: 63.
73. Ge S, Sailor KA, Ming GL, Song H (2008). Synaptic integration and plasticity of new neurons in the adult hippocampus. J Physiol 586: 3759-3765.
74. Ge S, Yang CH, Hsu KS, Ming GL, Song H (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54: 559-566. Young adult-born DGCs exhibit a critical period of enhanced synaptic plasticity in the hippocampus.
75. Gilbert PE, Kesner RP, Lee I (2001). Dissociating hippocampal subregions: double dissociation between dentate gyrus and CA1. Hippocampus 11: 626-636. Pioneering lesion study showing that the DG is necessary for resolving spatial interference.
76. Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP et al (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci 5: 1242-1247. Pioneering twin study suggesting that a smaller hippocampus confers a predisposition to stressrelated psychopathologies.
77. Gonzales RB, DeLeon Galvan CJ, Rangel YM, Claiborne BJ (2001). Distribution of thorny excrescences on CA3 pyramidal neurons in the rat hippocampus. J Comp Neurol 430: 357-368.
78. Goshen I (2014). The optogenetic revolution in memory research. Trends Neurosci 37: 511-522.
79. Goshen I, Brodsky M, Prakash R, Wallace J, Gradinaru V, Ramakrishnan C et al (2011). Dynamics of retrieval strategies for remote memories. Cell 147: 678-689. Study showing a continual role for the hippocampus in expression of remote contextual fear memory.
80. Gottesman II, Gould TD (2003). The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 160: 636-645.
81. Gray JA, McNaughton N (2000). The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System. 2nd edn. Oxford University Press: Oxford.
82. Grosenick L, Marshel JH, Deisseroth K (2015). Closed-loop and activity-guided optogenetic control. Neuron 86: 106-139.
83. Gross CT, Canteras NS (2012). The many paths to fear. Nat Rev Neurosci 13: 651-658.
84. Groves JO, Leslie I, Huang GJ, McHugh SB, Taylor A, Mott R et al (2013). Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model. PLoS Genet 9: e1003718.
85. Gu Y, Arruda-Carvalho M, Wang J, Janoschka SR, Josselyn SA, Frankland PW et al (2012). Optical controlling reveals time-dependent roles for adult-born dentate granule cells. Nat Neurosci 15: 1700-1706.
86. Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE, Adhikari A et al (2014). Natural neural projection dynamics underlying social behavior. Cell 157: 1535-1551.
87. Guzowski JF, Knierim JJ, Moser EI (2004). Ensemble dynamics of hippocampal regions CA3 and CA1. Neuron 44: 581-584.
88. Han JH, Kushner SA, Yiu AP, Cole CJ, Matynia A, Brown RA et al (2007). Neuronal competition and selection during memory formation. Science 316: 457-460.
89. Han JH, Kushner SA, Yiu AP, Hsiang HL, Buch T, Waisman A et al (2009). Selective erasure of a fear memory. Science 323: 1492-1496. First cellular instantiation of a memory engram.
90. Hardt O, Nader K, Nadel L (2013). Decay happens: the role of active forgetting in memory. Trends Cogn Sci 17: 111-120. Proposal discussing how time-dependent degradation of hippocampal memory traces influences cortical interference to promote fear overgeneralization.
91. Herry C, Johansen JP (2014). Encoding of fear learning and memory in distributed neuronal circuits. Nat Neurosci 17: 1644-1654.
92. 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; e-pub ahead of print).
93. Hinson RE (1982). Effects of UCS preexposure on excitatory and inhibitory rabbit eyelid conditioning: an associative effect of conditioned contextual stimuli. J Exp Psychol Anim Behav Process 8: 49-61.
94. Ho NF, Hooker JM, Sahay A, Holt DJ, Roffman JL (2013). In vivo imaging of adult human hippocampal neurogenesis: progress, pitfalls and promise. Mol Psychiatry 18: 404-416.
95. Holmes A, Singewald N (2013). Individual differences in recovery from traumatic fear. Trends Neurosci 36: 23-31.
96. Holtzheimer PE, Mayberg HS (2011). Deep brain stimulation for psychiatric disorders. Annu Rev Neurosci 34: 289-307.
97. Hsu PD, Lander ES, Zhang F (2014). Development and applications of CRISPRCas9 for genome engineering. Cell 157: 1262-1278.
98. Hyman SE (2014). Revitalizing psychiatric therapeutics. Neuropsychopharmacology 39: 220-229.
99. Ikrar T, Guo N, He K, Besnard A, Levinson S, Hill A et al (2013). Adult neurogenesis modifies excitability of the dentate gyrus. Front Neural Circuits 7: 204 Study showing blocking or enhancing adult hippocampal neurogenesis bidirectionally modifies excitability of the DG.
100. Iyengar SS, LaFrancois JJ, Friedman D, Drew LJ, Denny CA, Burghardt NS et al (2015). Suppression of adult neurogenesis increases the acute effects of kainic acid. Expl Neurol 264: 135-149.
101. Jennings JH, Ung RL, Resendez SL, Stamatakis AM, Taylor JG, Huang J et al (2015). Visualizing hypothalamic network dynamics for appetitive and consummatory behaviors. Cell 160: 516-527.
102. Jessberger S, Gage FH (2014). Adult neurogenesis: bridging the gap between mice and humans. Trends Cell Biol 24: 558-563.
103. Joels M, Baram TZ (2009). The neuro-symphony of stress. Nat Rev Neurosci 10: 459-466.
104. Jovanovic T, Ressler KJ (2010). How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am J Psychiatry 167: 648-662.
105. Jung MW, McNaughton BL (1993). Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3: 165-182. Dentate granule cells exhibit sparse, stable, and finely tuned place fields.
106. Kaouane N, Porte Y, Vallee M, Brayda-Bruno L, Mons N, Calandreau L et al (2012). Glucocorticoids can induce PTSD-like memory impairments in mice. Science 335: 1510-1513.
107. Kaplan MS, Hinds JW (1977). Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs. Science 197: 1092-1094.
108. Kempermann G (2008). The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? Trends Neurosci 31: 163-169.
109. Kesner RP (2013). Role of the hippocampus in mediating interference as measured by pattern separation processes. Behav Processes 93: 148-154.
110. Kheirbek MA, Drew LJ, Burghardt NS, Costantini DO, Tannenholz L, Ahmari SE et al (2013). Differential control of learning and anxiety along the dorsoventral axis of the dentate gyrus. Neuron 77: 955-968. Optogenetic inhibition of DGCs impairs conflict resolution in a place avoidance task.
111. Kheirbek MA, Klemenhagen KC, Sahay A, Hen R (2012b). Neurogenesis and generalization: a new approach to stratify and treat anxiety disorders. Nat Neurosci 15: 1613-1620.
112. Kheirbek MA, Tannenholz L, Hen R (2012a). NR2B-dependent plasticity of adult-born granule cells is necessary for context discrimination. J Neurosci 32: 8696-8702.
113. Kim J, Kwon JT, Kim HS, Josselyn SA, Han JH (2014). Memory recall and modifications by activating neurons with elevated CREB. Nat Neurosci 17: 65-72.
114. Kim JJ, Fanselow MS (1992). Modality-specific retrograde amnesia of fear. Science 256: 675-677.
115. Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A, Cho YK et al (2014). Independent optical excitation of distinct neural populations. Nat Methods 11: 338-346.
116. Knoth R, Singec I, Ditter M, Pantazis G, Capetian P, Meyer RP et al (2010). Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 5: e8809.
117. Koenen KC, Duncan LE, Liberzon I, Ressler KJ (2013). From candidate genes to genome-wide association: the challenges and promise of posttraumatic stress disorder genetic studies. Biol Psychiatry 74: 634-636.
118. Kostek JA, Beck KD, Gilbertson MW, Orr SP, Pang KC, Servatius RJ et al (2014). Acquired equivalence in U.S. veterans with symptoms of posttraumatic stress: reexperiencing symptoms are associated with greater generalization. J Trauma Stress 27: 717-720.
119. Kuhn HG, Dickinson-Anson H, Gage FH (1996). Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16: 2027-2033.
120. Kwapis JL, Wood MA (2014). Epigenetic mechanisms in fear conditioning: implications for treating post-traumatic stress disorder. Trends Neurosci 37: 706-720.
121. Lacefield CO, Itskov V, Reardon T, Hen R, Gordon JA (2012). Effects of adultgenerated granule cells on coordinated network activity in the dentate gyrus. Hippocampus 22: 106-116.
122. Lacy JW, Yassa MA, Stark SM, Muftuler LT, Stark CE (2011). Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity. Learn Mem 18: 15-18.
123. Laplagne DA, Esposito MS, Piatti VC, Morgenstern NA, Zhao C, van Praag H et al (2006). Functional convergence of neurons generated in the developing and adult hippocampus. PLoS Biol 4: e409.
124. Laplagne DA, Kamienkowski JE, Esposito MS, Piatti VC, Zhao C, Gage FH et al (2007). Similar GABAergic inputs in dentate granule cells born during embryonic and adult neurogenesis. Eur J Neurosci 25: 2973-2981.
125. Leboyer M, Bellivier F, Nosten-Bertrand M, Jouvent R, Pauls D, Mallet J (1998). Psychiatric genetics: search for phenotypes. Trends Neurosci 21: 102-105.
126. Lee I, Yoganarasimha D, Rao G, Knierim JJ (2004). Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3. Nature 430: 456-459.
127. Leutgeb JK, Leutgeb S, Moser MB, Moser EI (2007). Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315: 961-966. Study showing rate remapping underlies pattern separation in the DG as rats explore parametrically morphed environments.
128. Leutgeb JK, Leutgeb S, Treves A, Meyer R, Barnes CA, McNaughton BL et al (2005). Progressive transformation of hippocampal neuronal representations in 'morphed' environments. Neuron 48: 345-358.
129. Likhtik E, Gordon JA (2014). Circuits in sync: decoding theta communication in fear and safety. Neuropsychopharmacology 39: 235-236.
130. Lissek S (2012). Toward an account of clinical anxiety predicated on basic, neurally mapped mechanisms of Pavlovian fear-learning: the case for conditioned overgeneralization. Depress Anxiety 29: 257-263.
131. Lissek S, Grillon C (2012). Conditioning Models of PTSD. The Oxford Handbook of Traumatic Disorders. Oxford University Press.
132. Lissek S, van Meurs B (2014). Learning models of PTSD: theoretical accounts and psychobiological evidence. Int J Psychophysiol. pii: S0167-8760(14)01647-X. doi:10.1016/j.ijpsycho.2014.11.006; e-pub ahead of print.
133. Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K et al (2012). Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484: 381-385. Cellular instantiation of fear engram in the DG.
134. Lo L, Anderson DJ (2011). A Cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons. Neuron 72: 938-950.
135. Lovett-Barron M, Kaifosh P, Kheirbek MA, Danielson N, Zaremba JD, Reardon TR et al (2014). Dendritic inhibition in the hippocampus supports fear learning. Science 343: 857-863.
136. Luo AH, Tahsili-Fahadan P, Wise RA, Lupica CR, Aston-Jones G (2011). Linking context with reward: a functional circuit from hippocampal CA3 to ventral tegmental area. Science 333: 353-357.
137. Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10: 434-445.
138. Luthi A, Luscher C (2014). Pathological circuit function underlying addiction and anxiety disorders. Nat Neurosci 17: 1635-1643.
139. Magarinos AM, Verdugo JM, McEwen BS (1997). Chronic stress alters synaptic terminal structure in hippocampus. Proc Natl Acad Sci USA 94: 14002-14008.
140. Mahan AL, Ressler KJ (2012). Fear conditioning, synaptic plasticity and the amygdala: implications for posttraumatic stress disorder. Trends Neurosci 35: 24-35.
141. Malan-Muller S, Seedat S, Hemmings SM (2014). Understanding posttraumatic stress disorder: insights from the methylome. Genes Brain Behav 13: 52-68.
142. Manganas LN, Zhang X, Li Y, Hazel RD, Smith SD, Wagshul ME et al (2007). Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science 318: 980-985. Identification of metabolic biomarkers for detection and quantification of neural stem and progenitor cells in the human brain in vivo.
143. Maren S, Aharonov G, Fanselow MS (1997). Neurotoxic lesions of the dorsal hippocampus and Pavlovian fear conditioning in rats. Behav Brain Res 88: 261-274.
144. Maren S, Phan KL, Liberzon I (2013). The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat Rev Neurosci 14: 417-428.
145. Marin MF, Camprodon JA, Dougherty DD, Milad MR (2014). Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond. Depress Anxiety 31: 269-278.
146. Marin-Burgin A, Mongiat LA, Pardi MB, Schinder AF (2012). Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science 335: 1238-1242.
147. Marr D (1971). Simple memory: a theory for archicortex. Philos Trans R Soc Lond B Biol Sci 262: 23-81.
148. McAvoy K, Russo C, Kim S, Rankin G, Sahay A (2015). Fluoxetine induces inputspecific hippocampal dendritic spine remodeling along the septotemporal axis in adulthood and middle age. Hippocampus. (doi:10.1002/hipo.22464; e-pub ahead of print).
149. McAvoy K, Scobie KN, Berger F, Guo N, Vega-Ramirez H, Miake-Lye S et al (2014). Rejuvenating the dentate gyrus with stage-specific expansion of adult-born neurons to enhance memory precision in adulthood and aging. Soc Neurosci. Abstracts 2014, DP09.08/DP8.
150. McBain CJ (2008). Differential mechanisms of transmission and plasticity at mossy fiber synapses. Prog Brain Res 169: 225-240.
151. McCarroll SA, Hyman SE (2013). Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology. Neuron 80: 578-587.
152. McClelland JL, Goddard NH (1996). Considerations arising from a complementary learning systems perspective on hippocampus and neocortex. Hippocampus 6: 654-665. Computational model showing how sparseness in DG promotes storage of new information and separation of patterns in CA3.
153. McClelland JL, McNaughton BL, O'Reilly RC (1995). Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol Rev 102: 419-457.
154. McEwen BS (1999). Stress and hippocampal plasticity. Annu Rev Neurosci 22: 105-122.
155. McEwen BS (2000). Effects of adverse experiences for brain structure and function. Biol Psychiatry 48: 721-731.
156. McEwen BS, Eiland L, Hunter RG, Miller MM (2012). Stress and anxiety: structural plasticity and epigenetic regulation as a consequence of stress. Neuropharmacology 62: 3-12.
157. McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist JK et al (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science 317: 94-99. Genetic disruption of perforant path-DG synaptic plasticity impairs contextual fear discrimination and remapping of place cells in CA3.
158. McKenzie S, Eichenbaum H (2011). Consolidation and reconsolidation: two lives of memories? Neuron 71: 224-233.
159. McNaughton BL, Morris RG (1987). Hippocampal synaptic enhancement and information storage within a distributed memory system. Trends Neurosci 10: 408-415.
160. Milad MR, Quirk GJ (2012). Fear extinction as a model for translational neuroscience: ten years of progress. Annu Rev Psychol 63: 129-151.
161. Miller BR, Hen R (2015). The current state of the neurogenic theory of depression and anxiety. Curr Opin Neurobiol 30: 51-58.
162. Ming GL, Song H (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70: 687-702.
163. Nadel L, Moscovitch M (1997). Memory consolidation, retrograde amnesia and the hippocampal complex. Curr Opin Neurobiol 7: 217-227.
164. Nader K, Hardt O, Lanius R (2013). Memory as a new therapeutic target. Dialogues Clin Neurosci 15: 475-486.
165. Nakashiba T, Buhl DL, McHugh TJ, Tonegawa S (2009). Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron 62: 781-787. Study shows that genetic blockade of CA3 output impairs consolidation of contextual fear memory and ripple-related reactivation, thereby providing evidence for continued hippocampal engagement in consolidation of cortical traces.
166. Nakashiba T, Cushman JD, Pelkey KA, Renaudineau S, Buhl DL, McHugh TJ et al (2012). Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell 149: 188-201.
167. Nakashiba T, Young JZ, McHugh TJ, Buhl DL, Tonegawa S (2008). Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning. Science 319: 1260-1264.
168. Nakazawa K, Quirk MC, Chitwood RA, Watanabe M, Yeckel MF, Sun LD et al (2002). Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297: 211-218.
169. Neunuebel JP, Knierim JJ (2012). Spatial firing correlates of physiologically distinct cell types of the rat dentate gyrus. J Neurosci 32: 3848-3858.
170. Neunuebel JP, Knierim JJ (2014). CA3 retrieves coherent representations from degraded input: direct evidence for CA3 pattern completion and dentate gyrus pattern separation. Neuron 81: 416-427. Electrophysiological recordings of place cells showing that CA3 performs pattern completion and DG pattern separation in freely moving rats.
171. Neunuebel JP, Yoganarasimha D, Rao G, Knierim JJ (2013). Conflicts between local and global spatial frameworks dissociate neural representations of the lateral and medial entorhinal cortex. J Neurosci 33: 9246-9258.
172. Newman MG, Llera SJ, Erickson TM, Przeworski A, Castonguay LG (2013). Worry and generalized anxiety disorder: a review and theoretical synthesis of evidence on nature, etiology, mechanisms, and treatment. Annu Rev Clin Psychol 9: 275-297.
173. Neylan TC, Mueller SG, Wang Z, Metzler TJ, Lenoci M, Truran D et al (2010). Insomnia severity is associated with a decreased volume of the CA3/dentate gyrus hippocampal subfield. Biol Psychiatry 68: 494-496.
174. Nicoll RA, Schmitz D (2005). Synaptic plasticity at hippocampal mossy fibre synapses. Nat Rev Neurosci 6: 863-876.
175. Niibori Y, Yu TS, Epp JR, Akers KG, Josselyn SA, Frankland PW (2012). Suppression of adult neurogenesis impairs population coding of similar contexts in hippocampal CA3 region. Nat Commun 3: 1253 Study showing that genetic blockade of adult hippocampal neurogenesis impairs pattern separation in CA3.
176. O'Reilly RC, McClelland JL (1994). Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off. Hippocampus 4: 661-682.
177. Opendak M, Gould E (2015). Adult neurogenesis: a substrate for experiencedependent change. Trends Cogn Sci 19: 151-161.
178. Pan WX, McNaughton N (2004). The supramammillary area: its organization, functions and relationship to the hippocampus. Prog Neurobiol 74: 127-166.
179. Pan YW, Chan GC, Kuo CT, Storm DR, Xia Z (2012b). Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory. J Neurosci 32: 6444-6455. Inducible deletion of ERK5 in neurogenic regions abolishes adult hippocampal neurogenesis, accelerates memory decay, and decreases cognitive flexibility.
180. Pan YW, Storm DR, Xia Z (2012a). The maintenance of established remote contextual fear memory requires ERK5 MAP kinase and ongoing adult neurogenesis in the hippocampus. PLoS One 7: e50455.
181. Parsons RG, Ressler KJ (2013). Implications of memory modulation for posttraumatic stress and fear disorders. Nat Neurosci 16: 146-153.
182. Petrik D, Jiang Y, Birnbaum SG, Powell CM, Kim MS, Hsieh J et al (2012). Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule. FASEB J 26: 3148-3162.
183. Piatti VC, Ewell LA, Leutgeb JK (2013). Neurogenesis in the dentate gyrus: carrying the message or dictating the tone. Front Neurosci 7: 50.
184. Pickens CL, Golden SA, Adams-Deutsch T, Nair SG, Shaham Y (2009). Long-lasting incubation of conditioned fear in rats. Biol Psychiatry 65: 881-886.
185. Pieper AA, Xie S, Capota E, Estill SJ, Zhong J, Long JM et al (2010). Discovery of a proneurogenic, neuroprotective chemical. Cell 142: 39-51. The authors developed an in vivo screen and identified a novel, proneurogenic, neuroprotective compound that reverses age-related memory changes in hippocampus.
186. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW et al (2012). Biological studies of post-traumatic stress disorder. Nat Rev Neurosci 13: 769-787.
187. Popoli M, Yan Z, McEwen BS, Sanacora G (2012). The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13: 22-37.
188. Prudent V, Kumar A, Liu S, Wiggins G, Malaspina D, Gonen O (2010). Human hippocampal subfields in young adults at 7.0T: feasibility of imaging. Radiology 254: 900-906.
189. Ramirez S, Liu X, Lin PA, Suh J, Pignatelli M, Redondo RL et al (2013). Creating a false memory in the hippocampus. Science 341: 387-391.
190. Ramirez-Amaya V, Vazdarjanova A, Mikhael D, Rosi S, Worley PF, Barnes CA (2005). Spatial exploration-induced Arc mRNA and protein expression: evidence for selective, network-specific reactivation. J Neurosci 25: 1761-1768.
191. Rangel LM, Alexander AS, Aimone JB, Wiles J, Gage FH, Chiba AA et al (2014). Temporally selective contextual encoding in the dentate gyrus of the hippocampus. Nat Commun 5: 3181 Electrophysiological recordings of place cells showing that encoding of temporally separate events by DGCs is dependent on levels of adult hippocampal neurogenesis.
192. Rangel LM, Quinn LK, Chiba AA, Gage FH, Aimone JB (2013). A hypothesis for temporal coding of young and mature granule cells. Front Neurosci 7: 75.
193. Redondo RL, Kim J, Arons AL, Ramirez S, Liu X, Tonegawa S (2014). Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513: 426-430. The valence of a memory supported by 'engrambearing' cells in the DG can be rewritten by optogenetic manipulation.
194. Resendez SL, Stuber GD (2015). In vivo calcium imaging to illuminate neurocircuit activity dynamics underlying naturalistic behavior. Neuropsychopharmacology 40: 238-239.
195. Ressler KJ, Mayberg HS (2007). Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 10: 1116-1124.
196. Restivo L, Niibori Y, Wheeler AL, Josselyn SA, Frankland PW (2014). Functional, anatomical and effective connectivity with ca3 inhibitory interneurons underlies integration of newborn dentate gyrus cells into the adult hippocampus. Soc Neurosci. Abstracts 845.28/TT66.
197. Risold PY, Swanson LW (1997). Connections of the rat lateral septal complex. Brain Res Brain Res Rev 24: 115-195.
198. Rogerson T, Cai DJ, Frank A, Sano Y, Shobe J, Lopez-Aranda MF et al (2014). Synaptic tagging during memory allocation. Nat Rev Neurosci 15: 157-169.
199. Rolls ET (1996). A theory of hippocampal function in memory. Hippocampus 6: 601-620.
200. Ruediger S, Spirig D, Donato F, Caroni P (2012). Goal-oriented searching mediated by ventral hippocampus early in trial-and-error learning. Nat Neurosci 15: 1563-1571.
201. Ruediger S, Vittori C, Bednarek E, Genoud C, Strata P, Sacchetti B et al (2011). Learning-related feedforward inhibitory connectivity growth required for memory precision. Nature 473: 514-518. Study suggesting a role for hippocampal mossy fiber filopodial contacts with interneurons in governing timedependent fear generalization.
202. Sahay A, Scobie KN, Hill AS, O'Carroll CM, Kheirbek MA, Burghardt NS et al (2011b). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472: 466-470. Inducible depletion of the proapoptotic gene Bax in neural progenitors in the adult brain enhances hippocampal neurogenesis and discrimination of similar, but not distinct, contexts.
203. Sahay A, Wilson DA, Hen R (2011a). Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron 70: 582-588. Review proposing a role for adult hippocampal neurogenesis in modulating sparseness of activity in DG through feed-back inhibition.
204. Sanchez Alvarado A, Yamanaka S (2014). Rethinking differentiation: stem cells, regeneration, and plasticity. Cell 157: 110-119.
205. Sapolsky RM (2000). Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry 57: 925-935.
206. Satvat E, Schmidt B, Argraves M, Marrone DF, Markus EJ (2011). Changes in task demands alter the pattern of zif268 expression in the dentate gyrus. J Neurosci 31: 7163-7167. Resolving conflicting goals is associated with global remapping in the DG.
207. Sauerhofer E, Pamplona FA, Bedenk B, Moll GH, Dawirs RR, von Horsten S et al (2012). Generalization of contextual fear depends on associative rather than nonassociative memory components. Behav Brain Res 233: 483-493.
208. Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE et al (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA 103: 17501-17506.
209. Schloesser RJ, Jimenez DV, Hardy NF, Paredes D, Catlow BJ, Manji HK et al (2014). Atrophy of pyramidal neurons and increased stress-induced glutamate levels in CA3 following chronic suppression of adult neurogenesis. Brain Struct Funct 219: 1139-1148.
210. Schmidt B, Marrone DF, Markus EJ (2012a). Disambiguating the similar: the dentate gyrus and pattern separation. Behav Brain Res 226: 56-65.
211. Schmidt B, Satvat E, Argraves M, Markus EJ, Marrone DF (2012b). Cognitive demands induce selective hippocampal reorganization: arc expression in a place and response task. Hippocampus 22: 2114-2126.
212. Schmidt-Hieber C, Jonas P, Bischofberger J (2004). Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature 429: 184-187.
213. Schoenfeld TJ, Cameron HA (2015). Adult neurogenesis and mental illness. Neuropsychopharmacology 40: 113-128.
214. Schoenfeld TJ, Gould E (2013). Differential effects of stress and glucocorticoids on adult neurogenesis. Curr Top Behav Neurosci 15: 139-164.
215. Schoenfeld TJ, Rada P, Pieruzzini PR, Hsueh B, Gould E (2013). Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus. J Neurosci 33: 7770-7777.
216. Seri B, Garcia-Verdugo JM, McEwen BS, Alvarez-Buylla A (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci 21: 7153-7160.
217. Shin LM, Liberzon I (2010). The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology 35: 169-191.
218. Silva AJ, Zhou Y, Rogerson T, Shobe J, Balaji J (2009). Molecular and cellular approaches to memory allocation in neural circuits. Science 326: 391-395.
219. Singer BH, Gamelli AE, Fuller CL, Temme SJ, Parent JM, Murphy GG (2011). Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice. Proc Natl Acad Sci USA 108: 5437-5442.
220. Skinner DM, Martin GM, Wright SL, Tomlin J, Odintsova IV, Thorpe CM et al (2014). Hippocampal spatial mapping and the acquisition of competing responses. Hippocampus 24: 396-402.
221. Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM (2005). A role for adult neurogenesis in spatial long-term memory. Neuroscience 130: 843-852. First study showing that blockade of adult hippocampal neurogenesis decreases long-term spatial memory.
222. Snyder JS, Kee N, Wojtowicz JM (2001). Effects of adult neurogenesis on synaptic plasticity in the rat dentate gyrus. J Neurophysiol 85: 2423-2431.
223. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476: 458-461.
224. Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB et al (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell 153: 1219-1227. Pioneering study that used retrospective Carbon-14 birth dating to demonstrate that the human DG turns over throughout life.
225. Sparks FT, Lehmann H, Hernandez K, Sutherland RJ (2011). Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory. PLoS One 6: e27426.
226. Squire LR, Zola-Morgan S (1991). The medial temporal lobe memory system. Science 253: 1380-1386.
227. Strange BA, Duggins A, Penny W, Dolan RJ, Friston KJ (2005). Information theory, novelty and hippocampal responses: unpredicted or unpredictable? Neural Netw 18: 225-230.
228. Strange BA, Witter MP, Lein ES, Moser EI (2014). Functional organization of the hippocampal longitudinal axis. Nat Rev Neurosci 15: 655-669.
229. Sun Y, Nguyen AQ, Nguyen JP, Le L, Saur D, Choi J et al (2014). Cell-type-specific circuit connectivity of hippocampal CA1 revealed through Cre-dependent rabies tracing. Cell Rep 7: 269-280.
230. Surget A, Tanti A, Leonardo ED, Laugeray A, Rainer Q, Touma C et al (2011). Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry 16: 1177-1188.
231. Sutherland RJ, Lehmann H (2011). Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents. Curr Opin Neurobiol 21: 446-451.
232. Sutherland RJ, O'Brien J, Lehmann H (2008). Absence of systems consolidation of fear memories after dorsal, ventral, or complete hippocampal damage. Hippocampus 18: 710-718.
233. Swan AA, Clutton JE, Chary PK, Cook SG, Liu GG, Drew MR (2014). Characterization of the role of adult neurogenesis in touch-screen discrimination learning. Hippocampus 24: 1581-1591.
234. Takahashi K, Yamanaka S (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126: 663-676. First study demonstrating how mouse fibroblasts can be reprogrammed into induced pluripotent stem cells using 4 transcription factors.
235. Tanaka KZ, Pevzner A, Hamidi AB, Nakazawa Y, Graham J, Wiltgen BJ (2014). Cortical representations are reinstated by the hippocampus during memory retrieval. Neuron 84: 347-354.
236. Tannenholz L, Jimenez JC, Kheirbek MA (2014). Local and regional heterogeneity underlying hippocampal modulation of cognition and mood. Front Behav Neurosci 8: 147.
237. Tanti A, Belzung C (2013). Neurogenesis along the septo-temporal axis of the hippocampus: are depression and the action of antidepressants region-specific? Neuroscience 252: 234-252.
238. Tashiro A, Makino H, Gage FH (2007). Experience-specific functional modification of the dentate gyrus through adult neurogenesis: a critical period during an immature stage. J Neurosci 27: 3252-3259. Study suggesting that mature adult-born DGCs preferentially respond to inputs that they were previously exposed to during their maturation.
239. Teicher MH, Anderson CM, Polcari A (2012). Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc Natl Acad Sci USA 109: E563-E572.
240. Temprana SG, Mongiat LA, Yang SM, Trinchero MF, Alvarez DD, Kropff E et al (2015). Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells. Neuron 85: 116-130. Causal interrogation of feed-forward and feed-back inhibition recruited by adult-born DGCs at different stages of maturation ex vivo.
241. Teyler TJ, DiScenna P (1986). The hippocampal memory indexing theory. Behav Neurosci 100: 147-154. Influential proposal suggesting a role for the hippocampus in indexing neocortical memory representations.
242. Teyler TJ, Rudy JW (2007). The hippocampal indexing theory and episodic memory: updating the index. Hippocampus 17: 1158-1169.
243. Torborg CL, Nakashiba T, Tonegawa S, McBain CJ (2010). Control of CA3 output by feedforward inhibition despite developmental changes in the excitationinhibition balance. J Neurosci 30: 15628-15637.
244. Tovote P, Fadok JP, Luthi A (2015). Neuronal circuits for fear and anxiety. Nat Rev Neurosci 16: 317-331.
245. Tracey I, Flower R (2014). The warrior in the machine: neuroscience goes to war. Nat Rev Neurosci 15: 825-834.
246. Treves A, Rolls ET (1992). Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus 2: 189-199.
247. Tronel S, Belnoue L, Grosjean N, Revest JM, Piazza PV, Koehl M et al (2012). Adultborn neurons are necessary for extended contextual discrimination. Hippocampus 22: 292-298.
248. Trouche S, Bontempi B, Roullet P, Rampon C (2009). Recruitment of adultgenerated neurons into functional hippocampal networks contributes to updating and strengthening of spatial memory. Proc Natl Acad Sci USA 106: 5919-5924.
249. Tye KM (2014). Neural circuit reprogramming: a new paradigm for treating neuropsychiatric disease? Neuron 83: 1259-1261.
250. Tye KM, Deisseroth K (2012). Optogenetic investigation of neural circuits underlying brain disease in animal models. Nat Rev Neurosci 13: 251-266.
251. Vanni-Mercier G, Mauguiere F, Isnard J, Dreher JC (2009). The hippocampus codes the uncertainty of cue-outcome associations: an intracranial electrophysiological study in humans. J Neurosci 29: 5287-5294. Electrophysiological recordings in humans suggesting a role for the hippocampus in computing uncertainty signals for reward outcome probabilities.
252. Vazdarjanova A, Guzowski JF (2004). Differences in hippocampal neuronal population responses to modifications of an environmental context: evidence for distinct, yet complementary, functions of CA3 and CA1 ensembles. J Neurosci 24: 6489-6496. Pioneering study demonstrating using IEG-based cellular imaging approaches that global remapping occurs in CA3.
253. Voss MW, Vivar C, Kramer AF, van Praag H (2013). Bridging animal and human models of exercise-induced brain plasticity. Trends Cogn Sci 17: 525-544.
254. Walker AK, Rivera PD, Wang Q, Chuang JC, Tran S, Osborne-Lawrence S et al (2014). The P7C3 class of neuroprotective compounds exerts antidepressant efficacy in mice by increasing hippocampal neurogenesis. Mol Psychiatry 20: 500-508.
255. Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L et al (2012). Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 11: 23-35.
256. Wang SH, Morris RG (2010). Hippocampal-neocortical interactions in memory formation, consolidation, and reconsolidation. Annu Rev Psychol 61: 49-79 C41-44.
257. Wang SH, Teixeira CM, Wheeler AL, Frankland PW (2009). The precision of remote context memories does not require the hippocampus. Nat Neurosci 12: 253-255.
258. Wang W, Pan YW, Zou J, Li T, Abel GM, Palmiter RD et al (2014). Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampusdependent long-term memory. J Neurosci 34: 2130-2147. Inducible expression of a constitutively active ERK5 throughout adult-born DGC lineage, enhances cognitive flexibility, and extends hippocampal memory.
259. Wang Z, Neylan TC, Mueller SG, Lenoci M, Truran D, Marmar CR et al (2010). Magnetic resonance imaging of hippocampal subfields in posttraumatic stress disorder. Arch Gen Psychiatry 67: 296-303. Structural imaging study showing reduced DG-CA3 volumes in individuals with PTSD.
260. Wedeen VJ, Rosene DL, Wang R, Dai G, Mortazavi F, Hagmann P et al (2012). The geometric structure of the brain fiber pathways. Science 335: 1628-1634.
261. Wen Z, Nguyen HN, Guo Z, Lalli MA,Wang X, Su Y et al (2014). Synaptic dysregulation in a human iPS cell model of mental disorders. Nature 515: 414-418.
262. Wickersham IR, Lyon DC, Barnard RJ, Mori T, Finke S, Conzelmann KK et al (2007). Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons. Neuron 53: 639-647.
263. Widge AS, Dougherty DD, Moritz CT (2014). Affective brain-computer interfaces as enabling technology for responsive psychiatric stimulation. Brain Comput Interfaces (Abingdon) 1: 126-136.
264. Wiltgen BJ, Silva AJ (2007). Memory for context becomes less specific with time. Learn Mem 14: 313-317. Contextual fear memories generalize to novel, distinct contexts with time.
265. Wiltgen BJ, Zhou M, Cai Y, Balaji J, Karlsson MG, Parivash SN et al (2010). The hippocampus plays a selective role in the retrieval of detailed contextual memories. Curr Biol 20: 1336-1344.
266. Winocur G, Becker S, Luu P, Rosenzweig S, Wojtowicz JM (2012). Adult hippocampal neurogenesis and memory interference. Behav Brain Res 227: 464-469.
267. Winocur G, Moscovitch M, Sekeres M (2007). Memory consolidation or transformation: context manipulation and hippocampal representations of memory. Nat Neurosci 10: 555-557.
268. 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.
269. Wojtowicz JM, Askew ML, Winocur G (2008). The effects of running and of inhibiting adult neurogenesis on learning and memory in rats. Eur J Neurosci 27: 1494-1502.
270. Wu MV, Hen R (2014). Functional dissociation of adult-born neurons along the dorsoventral axis of the dentate gyrus. Hippocampus 24: 751-761.
271. Xia Z, Storm DR (2012). Role of signal transduction crosstalk between adenylyl cyclase and MAP kinase in hippocampus-dependent memory. Learn Mem 19: 369-374.
272. Yassa MA, Stark CE (2011). Pattern separation in the hippocampus. Trends Neurosci 34: 515-525.
273. Yehuda R, Daskalakis NP, Lehrner A, Desarnaud F, Bader HN, Makotkine I et al (2014). Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. Am J Psychiatry 171: 872-880.
274. Yehuda R, LeDoux J (2007). Response variation following trauma: a translational neuroscience approach to understanding PTSD. Neuron 56: 19-32.
275. Yiu AP, Mercaldo V, Yan C, Richards B, Rashid AJ, Hsiang HL et al (2014). Neurons are recruited to a memory trace based on relative neuronal excitability immediately before training. Neuron 83: 722-735.
276. Yu DX, Di Giorgio FP, Yao J, Marchetto MC, Brennand K, Wright R et al (2014). Modeling hippocampal neurogenesis using human pluripotent stem cells. Stem Cell Rep 2: 295-310.
277. Yu DX, Marchetto MC, Gage FH (2013). Therapeutic translation of iPSCs for treating neurological disease. Cell Stem Cell 12: 678-688.
278. Zhang CL, Zou Y, He W, Gage FH, Evans RM (2008). A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451: 1004-1007.
279. Zhang J, Ji F, Liu Y, Lei X, Li H, Ji G et al (2014). Ezh2 regulates adult hippocampal neurogenesis and memory. J Neurosci 34: 5184-5199.
280. Zhao C, Deng W, Gage FH (2008). Mechanisms and functional implications of adult neurogenesis. Cell 132: 645-660.
281. Zhou Y, Won J, Karlsson MG, Zhou M, Rogerson T, Balaji J et al (2009). CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nat Neurosci 12: 1438-1443.
282. Zitman FM, Lucas M, Trinks S, Grosse-Ophoff L, Kriebel M, Volkmer H et al (2014). Dentate gyrus local circuit is implicated in learning under stress-a role for neurofascin. Mol Neurobiol. (e-pub ahead of print).
283. Ziv Y, Burns LD, Cocker ED, Hamel EO, Ghosh KK, Kitch LJ et al (2013). Long-term dynamics of CA1 hippocampal place codes. Nat Neurosci 16: 264-266. Chronic calcium imaging in CA1 of freely moving mice allows decoding of place cells activity over time.
284. Zola-Morgan SM, Squire LR (1990). The primate hippocampal formation: evidence for a time-limited role in memory storage. Science 250: 288-290.
285. Zovkic IB, Sweatt JD (2013). Epigenetic mechanisms in learned fear: implications for PTSD. Neuropsychopharmacology 38: 77-93.