NR2B antagonist CP-101,606 abolishes pitch-mediated deviance detection in awake rats

Frontiers in Psychiatry

Volumn 5, Issue AUG, 2014, Pages

  Sivarao, Digavalli V ^a   Chen, Ping ^a   Yang, Yili ^a   Li, Yu Wen ^a   Pieschl, Rick ^a   Ahlijanian K , Michael ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

Auditory deviance; CP 101,606; Ketamine; Mismatch negativity; NMDA antagonist; NR2B

Indexed keywords

KETAMINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2B; TRAXOPRODIL;

ADULT; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUDITORY DEVIANCE DETECTION; CONTROLLED STUDY; DOSE RESPONSE; EVENT RELATED POTENTIAL; MALE; MISMATCH NEGATIVITY; NONHUMAN; PHARMACOLOGICAL PROCEDURES; PITCH; RAT; RODENT MODEL; SCHIZOPHRENIA; SENSORY SYSTEM; STIMULUS RESPONSE; WAKEFULNESS;

EID: 84905670569     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2014.00096     Document Type: Article

References (98)

1. Naatanen R, Kujala T, Winkler I. Auditory processing that leads to conscious perception: a unique window to central auditory processing opened by the mismatch negativity and related responses. Psychophysiology (2011) 48:4-22. doi: 10.1111/j.1469-8986.2010.01114.x
2. Naatanen R, Tervaniemi M, Sussman E, Paavilainen P, Winkler I. "Primitive intelligence" in the auditory cortex. Trends Neurosci (2001) 24:283-8. doi:10.1016/S0166-2236(00)01790-2
3. Shelley AM, Silipo G, Javitt DC. Diminished responsiveness of ERPs in schizophrenic subjects to changes in auditory stimulation parameters: implications for theories of cortical dysfunction. Schizophr Res (1999) 37:65-79.
4. Astikainen P, Stefanics G, Nokia M, Lipponen A, Cong F, Penttonen M, et al. Memory-based mismatch response to frequency changes in rats. PLoS One (2011) 6:e24208. doi:10.1371/journal.pone.0024208
5. Gil-da-Costa R, Stoner GR, Fung R, Albright TD. Nonhuman primate model of schizophrenia using a noninvasive EEG method. Proc Natl Acad Sci U S A (2013) 110:15425-30. doi:10.1073/pnas.1312264110
6. Javitt DC, Spencer KM, Thaker GK, Winterer G, Hajos M. Neurophysiological biomarkers for drug development in schizophrenia. Nat Rev Drug Discov (2008) 7:68-83. doi:10.1038/nrd2463
7. Todd J, Harms L, Schall U, Michie PT. Mismatch negativity: translating the potential. Front Psychiatry (2013) 4:171. doi:10.3389/fpsyt.2013.00171
8. Jemel B, Achenbach C, Muller BW, Ropcke B, Oades RD. Mismatch negativity results from bilateral asymmetric dipole sources in the frontal and temporal lobes. Brain Topogr (2002) 15:13-27. doi:10.1023/A:1019944805499
9. Kasai K, Nakagome K, Itoh K, Koshida I, Hata A, Iwanami A, et al. Multiple generators in the auditory automatic discrimination process in humans. Neuroreport (1999) 10:2267-71. doi:10.1097/00001756-199908020-00008
10. Miyanishi T, Sumiyoshi T, Higuchi Y, Seo T, Suzuki M. LORETA current source density for duration mismatch negativity and neuropsychological assessment in early schizophrenia. PLoS One (2013) 8:e61152. doi:10.1371/journal.pone.0061152
11. Molholm S, Martinez A, Ritter W, Javitt DC, Foxe JJ. The neural circuitry of pre-attentive auditory change-detection: an fMRI study of pitch and duration mismatch negativity generators. Cereb Cortex (2005) 15:545-51. doi:10.1093/CERCOR/BHH155
12. Naatanen R, Alho K. Generators of electrical and magnetic mismatch responses in humans. Brain Topogr (1995) 7:315-20. doi:10.1007/BF01195257
13. Oknina LB, Wild-Wall N, Oades RD, Juran SA, Röpcke B, Pfueller U, et al. Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset. Schizophr Res (2005) 76:25-41. doi:10.1016/j.schres.2004.10.003
14. Escera C, Malmierca MS. The auditory novelty system: an attempt to integrate human and animal research. Psychophysiology (2014) 51:111-23. doi:10.1111/psyp.12156
15. Nelken I, Yaron A, Polterovich A, Hershenhoren I. Stimulus-specific adaptation beyond pure tones. Adv Exp Med Biol (2013) 787:411-8. doi:10.1007/978-1-4614-1590-9_45
16. Näätänen R, Kujala T, Escera C, Baldeweg T, Kreegipuu K, Carlson S, et al. The mismatch negativity (MMN) - a unique window to disturbed central auditory processing in ageing and different clinical conditions. Clin Neurophysiol (2012) 123:424-58. doi:10.1016/j.clinph.2011.09.020
17. Naatanen R, Kujala T, Kreegipuu K, Carlson S, Escera C, Baldeweg T, et al. The mismatch negativity: an index of cognitive decline in neuropsychiatric and neurological diseases and in ageing. Brain (2011) 134:3435-53. doi:10.1093/brain/awr064
18. Light GA, Naatanen R. Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders. Proc Natl Acad Sci U S A (2013) 110:15175-6. doi:10.1073/pnas.1313287110
19. Lazar R, Metherate R. Spectral interactions, but no mismatch negativity, in auditory cortex of anesthetized rat. Hear Res (2003) 181:51-6. doi:10.1016/S0378-5955(03)00166-7
20. von der Behrens W, Bauerle P, Kossl M, Gaese BH. Correlating stimulus-specific adaptation of cortical neurons and local field potentials in the awake rat. J Neurosci (2009) 29:13837-49. doi:10.1523/JNEUROSCI.3475-09.2009
21. Ahmed M, Mällo T, Leppänen PH, Hämäläinen J, Ayräväinen L, Ruusuvirta T, et al. Mismatch brain response to speech sound changes in rats. Front Psychol (2011) 2:283. doi:10.3389/fpsyg.2011.00283
22. Nakamura T, Michie PT, Fulham WR, Todd J, Budd TW, Schall U, et al. Epidural auditory event-related potentials in the rat to frequency and duration deviants: evidence of mismatch negativity? Front Psychol (2011) 2:367. doi:10.3389/fpsyg.2011.00367
23. Shiramatsu TI, Kanzaki R, Takahashi H. Cortical mapping of mismatch negativity with deviance detection property in rat. PLoS One (2013) 8:e82663. doi:10.1371/journal.pone.0082663
24. Kraus N, McGee T, Carrell T, King C, Littman T, Nicol T. Discrimination of speech-like contrasts in the auditory thalamus and cortex. J Acoust Soc Am (1994) 96:2758-68. doi:10.1121/1.411282
25. Kraus N, McGee T, Littman T, Nicol T, King C. Nonprimary auditory thalamic representation of acoustic change. J Neurophysiol (1994) 72:1270-7.
26. Simpson GV, Knight RT. Multiple brain systems generating the rat auditory evoked potential. II. Dissociation of auditory cortex and non-lemniscal generator systems. Brain Res (1993) 602:251-63. doi:10.1016/0006-8993(93)90689-K
27. Simpson GV, Knight RT. Multiple brain systems generating the rat auditory evoked potential. I. Characterization of the auditory cortex response. Brain Res (1993) 602:240-50. doi:10.1016/0006-8993(93)90689-K
28. Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC. Role of cortical N-methyl-d-aspartate receptors in auditory sensory memory and mismatch negativity generation: implications for schizophrenia. Proc Natl Acad Sci U S A (1996) 93:11962-7. doi:10.1073/pnas.93.21.11962
29. Gunduz-Bruce H, Reinhart RM, Roach BJ, Gueorguieva R, Oliver S, D'Souza DC, et al. Glutamatergic modulation of auditory information processing in the human brain. Biol Psychiatry (2012) 71:969-77. doi:10.1016/j.biopsych.2011.09.031
30. Knott V, Shah D, Millar A, McIntosh J, Fisher D, Blais C, et al. Nicotine, auditory sensory memory, and sustained attention in a human ketamine model of schizophrenia: moderating influence of a hallucinatory trait. Front Pharmacol (2012) 3:172. doi:10.3389/fphar.2012.00172
31. Schmidt A, Bachmann R, Kometer M, Csomor PA, Stephan KE, Seifritz E, et al. Mismatch negativity encoding of prediction errors predicts S-ketamine-induced cognitive impairments. Neuropsychopharmacology (2012) 37:865-75. doi:10.1038/npp.2011.261
32. Umbricht D, Koller R, Vollenweider FX, Schmid L. Mismatch negativity predicts psychotic experiences induced by NMDA receptor antagonist in healthy volunteers. Biol Psychiatry (2002) 51:400-6. doi:10.1016/S0006-3223(01)01242-2
33. Umbricht D, Schmid L, Koller R, Vollenweider FX, Hell D, Javitt DC. Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia. Arch Gen Psychiatry (2000) 57:1139-47.
34. Huntley GW, Vickers JC, Morrison JH. Cellular and synaptic localization of NMDA and non-NMDA receptor subunits in neocortex: organizational features related to cortical circuitry, function and disease. Trends Neurosci (1994) 17:536-43. doi:10.1016/0166-2236(94)90158-9
35. Kohr G. NMDA receptor function: subunit composition versus spatial distribution. Cell Tissue Res (2006) 326:439-46. doi:10.1007/s00441-006-0273-6
36. Mony L, Kew JN, Gunthorpe MJ, Paoletti P. Allosteric modulators of NR2B-containing NMDA receptors: molecular mechanisms and therapeutic potential. Br J Pharmacol (2009) 157:1301-17. doi:10.1111/j.1476-5381.2009.00304.x
37. Santangelo RM, Acker TM, Zimmerman SS, Katzman BM, Strong KL, Traynelis SF, et al. Novel NMDA receptor modulators: an update. Expert Opin Ther Pat (2012) 22:1337-52. doi:10.1517/13543776.2012.728587
38. Brigman JL, Daut RA, Wright T, Gunduz-Cinar O, Graybeal C, Davis MI, et al. GluN2B in corticostriatal circuits governs choice learning and choice shifting. Nat Neurosci (2013) 16:1101-10. doi:10.1038/nn.3457
39. Dalton GL, Ma LM, Phillips AG, Floresco SB. Blockade of NMDA GluN2B receptors selectively impairs behavioral flexibility but not initial discrimination learning. Psychopharmacology (Berl) (2011) 216:525-35. doi:10.1007/s00213-011-2246-z
40. Wang H, Stradtman GG III, Wang XJ, Gao WJ. A specialized NMDA receptor function in layer 5 recurrent microcircuitry of the adult rat prefrontal cortex. Proc Natl Acad Sci U S A (2008) 105:16791-6. doi:10.1073/pnas.0804318105
41. Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, et al. NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex. Neuron (2013) 77:736-49. doi:10.1016/j.neuron.2012.12.032
42. Alain C, Woods DL, Knight RT. A distributed cortical network for auditory sensory memory in humans. Brain Res (1998) 812:23-37.
43. Alho K, Woods DL, Algazi A, Knight RT, Naatanen R. Lesions of frontal cortex diminish the auditory mismatch negativity. Electroencephalogr Clin Neurophysiol (1994) 91:353-62. doi:10.1016/0013-4694(94)00173-1
44. Doeller CF, Opitz B, Mecklinger A, Krick C, Reith W, Schröger E. Prefrontal cortex involvement in preattentive auditory deviance detection: neuroimaging and electrophysiological evidence. Neuroimage (2003) 20:1270-82. doi:10.1016/S1053-8119(03)00389-6
45. Light GA, Braff DL. Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. Arch Gen Psychiatry (2005) 62:127-36. doi:10.1001/archpsyc.62.2.127
46. Opitz B, Rinne T, Mecklinger A, von Cramon DY, Schroger E. Differential contribution of frontal and temporal cortices to auditory change detection: fMRI and ERP results. Neuroimage (2002) 15:167-74. doi:10.1006/nimg.2001.0970
47. Martin BA, Tremblay KL, Korczak P. Speech evoked potentials: from the laboratory to the clinic. Ear Hear (2008) 29:285-313. doi:10.1097/AUD.0b013e3181662c0e
48. Herrmann CS, Knight RT. Mechanisms of human attention: event-related potentials and oscillations. Neurosci Biobehav Rev (2001) 25:465-76. doi:10.1016/S0149-7634(01)00027-6
49. Woldorff MG, Hillyard SA. Modulation of early auditory processing during selective listening to rapidly presented tones. Electroencephalogr Clin Neurophysiol (1991) 79:170-91.
50. Dias EC, Butler PD, Hoptman MJ, Javitt DC. Early sensory contributions to contextual encoding deficits in schizophrenia. Arch Gen Psychiatry (2011) 68:654-64. doi:10.1001/archgenpsychiatry.2011.17
51. Hall MH, Levy DL, Salisbury DF, Haddad S, Gallagher P, Lohan M, et al. Neurophysiologic effect of GWAS derived schizophrenia and bipolar risk variants. Am J Med Genet B Neuropsychiatr Genet (2014) 165:9-18. doi:10.1002/ajmg.b.32212
52. Salisbury DF, Collins KC, McCarley RW. Reductions in the N1 and P2 auditory event-related potentials in first-hospitalized and chronic schizophrenia. Schizophr Bull (2010) 36:991-1000. doi:10.1093/schbul/sbp003
53. Amann LC, Gandal MJ, Halene TB, Ehrlichman RS, White SL, McCarren HS, et al. Mouse behavioral endophenotypes for schizophrenia. Brain Res Bull (2010) 83:147-61. doi:10.1016/j.brainresbull.2010.04.008
54. Umbricht D, Vyssotky D, Latanov A, Nitsch R, Brambilla R, D'Adamo P, et al. Midlatency auditory event-related potentials in mice: comparison to midlatency auditory ERPs in humans. Brain Res (2004) 1019:189-200. doi:10.1016/j.brainres.2004.05.097
55. Oranje B, van Berckel BN, Kemner C, van Ree JM, Kahn RS, Verbaten MN. The effects of a sub-anaesthetic dose of ketamine on human selective attention. Neuropsychopharmacology (2000) 22:293-302. doi:10.1016/S0893-133X(99)00118-9
56. Ehrlichman RS, Maxwell CR, Majumdar S, Siegel SJ. Deviance-elicited changes in event-related potentials are attenuated by ketamine in mice. J Cogn Neurosci (2008) 20:1403-14. doi:10.1162/jocn.2008.20097
57. Maxwell CR, Ehrlichman RS, Liang Y, Trief D, Kanes SJ, Karp J, et al. Ketamine produces lasting disruptions in encoding of sensory stimuli. J Pharmacol Exp Ther (2006) 316:315-24. doi:10.1124/jpet.105.091199
58. Luck SJ. An Introduction to the Event-Related Potential Technique. Cambridge, MA: MIT Press (2004). 388 p.
59. Fischer G, Mutel V, Trube G, Malherbe P, Kew JN, Mohacsi E, et al. Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro. J Pharmacol Exp Ther (1997) 283:1285-92.
60. Lord B, Wintmolders C, Langlois X, Nguyen L, Lovenberg T, Bonaventure P. Comparison of the ex vivo receptor occupancy profile of ketamine to several NMDA receptor antagonists in mouse hippocampus. Eur J Pharmacol (2013) 715:21-5. doi:10.1016/j.ejphar.2013.06.028
61. Murray F, Kennedy J, Hutson PH, Elliot J, Huscroft I, Mohnen K, et al. Modulation of [3H]MK-801 binding to NMDA receptors in vivo and in vitro. Eur J Pharmacol (2000) 397:263-70. doi:10.1016/S0014-2999(00)00263-6
62. Jung F, Stephan KE, Backes H, Moran R, Gramer M, Kumagai T, et al. Mismatch responses in the awake rat: evidence from epidural recordings of auditory cortical fields. PLoS One (2013) 8:e63203. doi:10.1371/journal.pone.0063203
63. Ruusuvirta T, Lipponen A, Pellinen E, Penttonen M, Astikainen P. Auditory cortical and hippocampal-system mismatch responses to duration deviants in urethane-anesthetized rats. PLoS One (2013) 8:e54624. doi:10.1371/journal.pone.0054624
64. Jacobsen T, Schroger E. Is there pre-attentive memory-based comparison of pitch? Psychophysiology (2001) 38:723-7. doi:10.1111/1469-8986.3840723
65. King C, McGee T, Rubel EW, Nicol T, Kraus N. Acoustic features and acoustic changes are represented by different central pathways. Hear Res (1995) 85:45-52.
66. Scherg M, Vajsar J, Picton TW. A source analysis of the late human auditory evoked potentials. J Cogn Neurosci (1989) 1:336-55. doi:10.1162/jocn.1989.1.4.336
67. Alho K. Cerebral generators of mismatch negativity (MMN) and its magnetic counterpart (MMNm) elicited by sound changes. Ear Hear (1995) 16:38-51.
68. Escera C, Alho K, Winkler I, Naatanen R. Neural mechanisms of involuntary attention to acoustic novelty and change. J Cogn Neurosci (1998) 10:590-604. doi:10.1162/089892998562997
69. Garrido MI, Kilner JM, Stephan KE, Friston KJ. The mismatch negativity: a review of underlying mechanisms. Clin Neurophysiol (2009) 120:453-63. doi:10.1016/j.clinph.2008.11.029
70. May PJ, Tiitinen H. Mismatch negativity (MMN), the deviance-elicited auditory deflection, explained. Psychophysiology (2010) 47:66-122. doi:10.1111/j.1469-8986.2009.00856.x
71. Jaaskelainen IP, Ahveninen J, Bonmassar G, Dale AM, Ilmoniemi RJ, Levänen S, et al. Human posterior auditory cortex gates novel sounds to consciousness. Proc Natl Acad Sci U S A (2004) 101:6809-14. doi:10.1073/pnas.0303760101
72. Antunes FM, Malmierca MS. An overview of stimulus-specific adaptation in the auditory thalamus. Brain Topogr (2014) 27:480-99. doi:10.1007/s10548-013-0342-6
73. Ayala YA, Malmierca MS. Stimulus-specific adaptation and deviance detection in the inferior colliculus. Front Neural Circuits (2012) 6:89. doi:10.3389/fncir.2012.00089
74. Grimm S, Escera C. Auditory deviance detection revisited: evidence for a hierarchical novelty system. Int J Psychophysiol (2012) 85:88-92. doi:10.1016/j.ijpsycho.2011.05.012
75. Escera C, Leung S, Grimm S. Deviance detection based on regularity encoding along the auditory hierarchy: electrophysiological evidence in humans. Brain Topogr (2014) 27:527-38. doi:10.1007/s10548-013-0328-4
76. Heekeren K, Daumann J, Neukirch A, Stock C, Kawohl W, Norra C, et al. Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis. Psychopharmacology (Berl) (2008) 199:77-88. doi:10.1007/s00213-008-1129-4
77. Tikhonravov D, Neuvonen T, Pertovaara A, Savioja K, Ruusuvirta T, Näätänen R, et al. Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in anesthetized rats. Brain Res (2008) 1203:97-102. doi:10.1016/j.brainres.2008.02.006
78. Mathalon DH, Ahn KH, Perry EB Jr, Cho HS, Roach BJ, Blais RK, et al. Effects of nicotine on the neurophysiological and behavioral effects of ketamine in humans. Front Psychiatry (2014) 5:3. doi:10.3389/fpsyt.2014.00003
79. Roser P, Haussleiter IS, Chong HJ, Maier C, Kawohl W, Norra C, et al. Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia. Psychopharmacology (Berl) (2011) 218:611-20. doi:10.1007/s00213-011-2352-y
80. Plourde G, Baribeau J, Bonhomme V. Ketamine increases the amplitude of the 40-Hz auditory steady-state response in humans. Br J Anaesth (1997) 78:524-9. doi:10.1093/bja/78.5.524
81. Schubert A, Licina MG, Lineberry PJ. The effect of ketamine on human somatosensory evoked potentials and its modification by nitrous oxide. Anesthesiology (1990) 72:33-9. doi:10.1097/00000542-199001000-00007
82. Moghaddam B, Adams B, Verma A, Daly D. Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci (1997) 17:2921-7.
83. Kreitschmann-Andermahr I, Rosburg T, Demme U, Gaser E, Nowak H, Sauer H. Effect of ketamine on the neuromagnetic mismatch field in healthy humans. Brain Res Cogn Brain Res (2001) 12:109-16. doi:10.1016/S0926-6410(01)00043-X
84. Pineda JA, Holmes TC, Swick D, Foote SL. Brain-stem auditory evoked potentials in squirrel monkey (Saimiri sciureus). Electroencephalogr Clin Neurophysiol (1989) 73:532-43. doi:10.1016/0013-4694(89)90262-9
85. Rennaker RL, Carey HL, Anderson SE, Sloan AM, Kilgard MP. Anesthesia suppresses nonsynchronous responses to repetitive broadband stimuli. Neuroscience (2007) 145:357-69. doi:10.1016/j.neuroscience.2006.11.043
86. Kittelberger K, Hur EE, Sazegar S, Keshavan V, Kocsis B. Comparison of the effects of acute and chronic administration of ketamine on hippocampal oscillations: relevance for the NMDA receptor hypofunction model of schizophrenia. Brain Struct Funct (2012) 217:395-409. doi:10.1007/s00429-011-0351-8
87. Lazarewicz MT, Ehrlichman RS, Maxwell CR, Gandal MJ, Finkel LH, Siegel SJ. Ketamine modulates theta and gamma oscillations. J Cogn Neurosci (2010) 22:1452-64. doi:10.1162/jocn.2009.21305
88. Menniti F, Chenard B, Collins M, Ducat M, Shalaby I, White F. CP-101,606, a potent neuroprotectant selective for forebrain neurons. Eur J Pharmacol (1997) 331:117-26. doi:10.1016/S0014-2999(97)10092-9
89. Taniguchi K, Shinjo K, Mizutani M, Shimada K, Ishikawa T, Menniti FS, et al. Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist. Br J Pharmacol (1997) 122:809-12.
90. Yago E, Escera C, Alho K, Giard MH. Cerebral mechanisms underlying orienting of attention towards auditory frequency changes. Neuroreport (2001) 12:2583-7.
91. Javitt DC. When doors of perception close: bottom-up models of disrupted cognition in schizophrenia. Annu Rev Clin Psychol (2009) 5:249-75. doi:10.1146/annurev.clinpsy.032408.153502
92. Light GA, Braff DL. Stability of mismatch negativity deficits and their relationship to functional impairments in chronic schizophrenia. Am J Psychiatry (2005) 162:1741-3. doi:10.1176/appi.ajp.162.9.1741
93. Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, et al. Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. Trends Neurosci (2008) 31:234-42. doi:10.1016/j.tins.2008.02.005
94. Arnsten AF. Prefrontal cortical network connections: key site of vulnerability in stress and schizophrenia. Int J Dev Neurosci (2011) 29:215-23. doi:10.1016/j.ijdevneu.2011.02.006
95. Lett TA, Voineskos AN, Kennedy JL, Levine B, Daskalakis ZJ. Treating working memory deficits in schizophrenia: a review of the neurobiology. Biol Psychiatry (2014) 75:361-70. doi:10.1016/j.biopsych.2013.07.026
96. Cui Y, Jin J, Zhang X, Xu H, Yang L, Du D, et al. Forebrain NR2B overexpression facilitating the prefrontal cortex long-term potentiation and enhancing working memory function in mice. PLoS One (2011) 6:e20312. doi:10.1371/journal.pone.0020312
97. Gilmartin MR, Kwapis JL, Helmstetter FJ. NR2A- and NR2B-containing NMDA receptors in the prelimbic medial prefrontal cortex differentially mediate trace, delay, and contextual fear conditioning. Learn Mem (2013) 20:290-4. doi:10.1101/lm.030510.113
98. Kristiansen LV, Bakir B, Haroutunian V, Meador-Woodruff JH. Expression of the NR2B-NMDA receptor trafficking complex in prefrontal cortex from a group of elderly patients with schizophrenia. Schizophr Res (2010) 119:198-209. doi:10.1016/j.schres.2010.02.1069