Advertisement

Pyramidal Cell Selective Ablation of N-Methyl-D-Aspartate Receptor 1 Causes Increase in Cellular and Network Excitability

      Abstract

      Background

      Neuronal activity at gamma frequency is impaired in schizophrenia (SZ) and is considered critical for cognitive performance. Such impairments are thought to be due to reduced N-methyl-D-aspartate receptor (NMDAR)-mediated inhibition from parvalbumin interneurons, rather than a direct role of impaired NMDAR signaling on pyramidal neurons. However, recent studies suggest a direct role of pyramidal neurons in regulating gamma oscillations. In particular, a computational model has been proposed in which phasic currents from pyramidal cells could drive synchronized feedback inhibition from interneurons. As such, impairments in pyramidal neuron activity could lead to abnormal gamma oscillations. However, this computational model has not been tested experimentally and the molecular mechanisms underlying pyramidal neuron dysfunction in SZ remain unclear.

      Methods

      In the present study, we tested the hypothesis that SZ-related phenotypes could arise from reduced NMDAR signaling in pyramidal neurons using forebrain pyramidal neuron specific NMDA receptor 1 knockout mice.

      Results

      The mice displayed increased baseline gamma power, as well as sociocognitive impairments. These phenotypes were associated with increased pyramidal cell excitability due to changes in inherent membrane properties. Interestingly, mutant mice showed decreased expression of GIRK2 channels, which has been linked to increased neuronal excitability.

      Conclusions

      Our data demonstrate for the first time that NMDAR hypofunction in pyramidal cells is sufficient to cause electrophysiological, molecular, neuropathological, and behavioral changes related to SZ.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Gonzalez-Burgos G.
        • Lewis D.A.
        NMDA receptor hypofunction, parvalbumin-positive neurons and cortical gamma oscillations in schizophrenia.
        Schizophr Bull. 2012; 38: 950-957
        • Hamm J.P.
        • Gilmore C.S.
        • Picchetti N.A.
        • Sponheim S.R.
        • Clementz B.A.
        Abnormalities of neuronal oscillations and temporal integration to low- and high-frequency auditory stimulation in schizophrenia.
        Biol Psychiatry. 2011; 69: 989-996
        • Kirihara K.
        • Rissling A.J.
        • Swerdlow N.R.
        • Braff D.L.
        • Light G.A.
        Hierarchical organization of gamma and theta oscillatory dynamics in schizophrenia.
        Biol Psychiatry. 2012; 71: 873-880
        • Gandal M.J.
        • Edgar J.C.
        • Klook K.
        • Siegel S.J.
        Gamma synchrony: Towards a translational biomarker for the treatment-resistant symptoms of schizophrenia.
        Neuropharmacology. 2012; 62: 1504-1518
        • Hong L.E.
        • Summerfelt A.
        • Mitchell B.D.
        • McMahon R.P.
        • Wonodi I.
        • Buchanan R.W.
        • Thaker G.K.
        Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate.
        Arch Gen Psychiatry. 2008; 65: 1008-1016
        • Winterer G.
        • Coppola R.
        • Goldberg T.E.
        • Egan M.F.
        • Jones D.W.
        • Sanchez C.E.
        • Weinberger D.R.
        Prefrontal broadband noise, working memory, and genetic risk for schizophrenia.
        Am J Psychiatry. 2004; 161: 490-500
        • Basar-Eroglu C.
        • Schmiedt-Fehr C.
        • Mathes B.
        • Zimmermann J.
        • Brand A.
        Are oscillatory brain responses generally reduced in schizophrenia during long sustained attentional processing?.
        Int J Psychophysiol. 2009; 71: 75-83
        • Hall M.H.
        • Taylor G.
        • Salisbury D.F.
        • Levy D.L.
        Sensory gating event-related potentials and oscillations in schizophrenia patients and their unaffected relatives.
        Schizophr Bull. 2011; 37: 1187-1199
        • Hall M.H.
        • Taylor G.
        • Sham P.
        • Schulze K.
        • Rijsdijk F.
        • Picchioni M.
        • et al.
        The early auditory gamma-band response is heritable and a putative endophenotype of schizophrenia.
        Schizophr Bull. 2011; 37: 778-787
        • Lee K.H.
        • Williams L.M.
        • Haig A.
        • Goldberg E.
        • Gordon E.
        An integration of 40 Hz Gamma and phasic arousal: Novelty and routinization processing in schizophrenia.
        Clin Neurophysiol. 2001; 112: 1499-1507
        • Leicht G.
        • Karch S.
        • Karamatskos E.
        • Giegling I.
        • Moller H.J.
        • Hegerl U.
        • et al.
        Alterations of the early auditory evoked gamma-band response in first-degree relatives of patients with schizophrenia: Hints to a new intermediate phenotype.
        J Psychiatr Res. 2011; 45: 699-705
        • Leicht G.
        • Kirsch V.
        • Giegling I.
        • Karch S.
        • Hantschk I.
        • Moller H.J.
        • et al.
        Reduced early auditory evoked gamma-band response in patients with schizophrenia.
        Biol Psychiatry. 2010; 67: 224-231
        • Lenz D.
        • Fischer S.
        • Schadow J.
        • Bogerts B.
        • Herrmann C.S.
        Altered evoked gamma-band responses as a neurophysiological marker of schizophrenia?.
        Int J Psychophysiol. 2011; 79: 25-31
        • Teale P.
        • Collins D.
        • Maharajh K.
        • Rojas D.C.
        • Kronberg E.
        • Reite M.
        Cortical source estimates of gamma band amplitude and phase are different in schizophrenia.
        Neuroimage. 2008; 42: 1481-1489
        • Atallah B.V.
        • Scanziani M.
        Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition.
        Neuron. 2009; 62: 566-577
        • Economo M.N.
        • White J.A.
        Membrane properties and the balance between excitation and inhibition control gamma-frequency oscillations arising from feedback inhibition.
        PLoS Comput Biol. 2012; 8: e1002354
        • Yizhar O.
        • Fenno L.E.
        • Prigge M.
        • Schneider F.
        • Davidson T.J.
        • O’Shea D.J.
        • et al.
        Neocortical excitation/inhibition balance in information processing and social dysfunction.
        Nature. 2011; 477: 171-178
        • Ford J.M.
        • Krystal J.H.
        • Mathalon D.H.
        Neural synchrony in schizophrenia: From networks to new treatments.
        Schizophr Bull. 2007; 33: 848-852
        • Hashimoto T.
        • Arion D.
        • Unger T.
        • Maldonado-Aviles J.G.
        • Morris H.M.
        • Volk D.W.
        • et al.
        Alterations in GABA-related transcriptome in the dorsolateral prefrontal cortex of subjects with schizophrenia.
        Mol Psychiatry. 2008; 13: 147-161
        • Hashimoto T.
        • Volk D.W.
        • Eggan S.M.
        • Mirnics K.
        • Pierri J.N.
        • Sun Z.
        • et al.
        Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia.
        J Neurosci. 2003; 23: 6315-6326
        • Mellios N.
        • Huang H.S.
        • Baker S.P.
        • Galdzicka M.
        • Ginns E.
        • Akbarian S.
        Molecular determinants of dysregulated GABAergic gene expression in the prefrontal cortex of subjects with schizophrenia.
        Biol Psychiatry. 2009; 65: 1006-1014
        • Homayoun H.
        • Moghaddam B.
        NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons.
        J Neurosci. 2007; 27: 11496-11500
        • Korotkova T.
        • Fuchs E.C.
        • Ponomarenko A.
        • von Engelhardt J.
        • Monyer H.
        NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial representations, and working memory.
        Neuron. 2010; 68: 557-569
        • Carlen M.
        • Meletis K.
        • Siegle J.H.
        • Cardin J.A.
        • Futai K.
        • Vierling-Claassen D.
        • et al.
        A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior.
        Mol Psychiatry. 2012; 17: 537-548
        • Xue J.G.
        • Masuoka T.
        • Gong X.D.
        • Chen K.S.
        • Yanagawa Y.
        • Law S.K.
        • Konishi S.
        NMDA receptor activation enhances inhibitory GABAergic transmission onto hippocampal pyramidal neurons via presynaptic and postsynaptic mechanisms.
        J Neurophysiol. 2011; 105: 2897-2906
        • Javitt D.C.
        • Zukin S.R.
        Recent advances in the phencyclidine model of schizophrenia.
        Am J Psychiatry. 1991; 148: 1301-1308
        • Jentsch J.D.
        • Andrusiak E.
        • Tran A.
        • Bowers Jr, M.B.
        • Roth R.H.
        Delta 9-tetrahydrocannabinol increases prefrontal cortical catecholaminergic utilization and impairs spatial working memory in the rat: Blockade of dopaminergic effects with HA966.
        Neuropsychopharmacology. 1997; 16: 426-432
        • Krystal J.H.
        • Karper L.P.
        • Seibyl J.P.
        • Freeman G.K.
        • Delaney R.
        • Bremner J.D.
        • et al.
        Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses.
        Arch Gen Psychiatry. 1994; 51: 199-214
        • Lahti A.C.
        • Koffel B.
        • LaPorte D.
        • Tamminga C.A.
        Subanesthetic doses of ketamine stimulate psychosis in schizophrenia.
        Neuropsychopharmacology. 1995; 13: 9-19
        • Lahti A.C.
        • Weiler M.A.
        • Tamara Michaelidis B.A.
        • Parwani A.
        • Tamminga C.A.
        Effects of ketamine in normal and schizophrenic volunteers.
        Neuropsychopharmacology. 2001; 25: 455-467
        • Stone J.M.
        • Erlandsson K.
        • Arstad E.
        • Squassante L.
        • Teneggi V.
        • Bressan R.A.
        • et al.
        Relationship between ketamine-induced psychotic symptoms and NMDA receptor occupancy: A [(123)I]CNS-1261 SPET study.
        Psychopharmacology (Berl). 2008; 197: 401-408
        • Bickel S.
        • Lipp H.P.
        • Umbricht D.
        Impaired attentional modulation of auditory evoked potentials in N-methyl-D-aspartate NR1 hypomorphic mice.
        Genes Brain Behav. 2007; 6: 558-568
        • Duncan G.
        • Miyamoto S.
        • Gu H.
        • Lieberman J.
        • Koller B.
        • Snouwaert J.
        Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function.
        Brain Res. 2002; 951: 166-176
        • Duncan G.E.
        • Moy S.S.
        • Perez A.
        • Eddy D.M.
        • Zinzow W.M.
        • Lieberman J.A.
        • et al.
        Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function.
        Behav Brain Res. 2004; 153: 507-519
        • Dzirasa K.
        • Ramsey A.J.
        • Takahashi D.Y.
        • Stapleton J.
        • Potes J.M.
        • Williams J.K.
        • et al.
        Hyperdopaminergia and NMDA receptor hypofunction disrupt neural phase signaling.
        J Neurosci. 2009; 29: 8215-8224
        • Halene T.B.
        • Ehrlichman R.S.
        • Liang Y.
        • Christian E.P.
        • Jonak G.J.
        • Gur T.L.
        • et al.
        Assessment of NMDA receptor NR1 subunit hypofunction in mice as a model for schizophrenia.
        Genes Brain Behav. 2009; 8: 661-675
        • Mohn A.R.
        • Gainetdinov R.R.
        • Caron M.G.
        • Koller B.H.
        Mice with reduced NMDA receptor expression display behaviors related to schizophrenia.
        Cell. 1999; 98: 427-436
        • Gandal M.J.
        • Sisti J.
        • Klook K.
        • Ortinski P.I.
        • Leitman V.
        • Liang Y.
        • et al.
        GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.
        Transl Psychiatry. 2012; 2: e142
        • Li C.
        • Niu W.
        • Jiang C.H.
        • Hu Y.
        Effects of enriched environment on gene expression and signal pathways in cortex of hippocampal CA1 specific NMDAR1 knockout mice.
        Brain Res Bull. 2007; 71: 568-577
        • McHugh T.J.
        • Blum K.I.
        • Tsien J.Z.
        • Tonegawa S.
        • Wilson M.A.
        Impaired hippocampal representation of space in CA1-specific NMDAR1 knockout mice.
        Cell. 1996; 87: 1339-1349
        • Rampon C.
        • Tang Y.P.
        • Goodhouse J.
        • Shimizu E.
        • Kyin M.
        • Tsien J.Z.
        Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice.
        Nat Neurosci. 2000; 3: 238-244
        • Tsien J.Z.
        • Chen D.F.
        • Gerber D.
        • Tom C.
        • Mercer E.H.
        • Anderson D.J.
        • et al.
        Subregion- and cell type-restricted gene knockout in mouse brain.
        Cell. 1996; 87: 1317-1326
        • Wang H.Y.
        • Friedman E.
        Enhanced protein kinase C activity and translocation in bipolar affective disorder brains.
        Biol Psychiatry. 1996; 40: 568-575
        • Sankoorikal G.M.
        • Kaercher K.A.
        • Boon C.J.
        • Lee J.K.
        • Brodkin E.S.
        A mouse model system for genetic analysis of sociability: C57BL/6J versus BALB/cJ inbred mouse strains.
        Biol Psychiatry. 2006; 59: 415-423
        • Deacon R.M.
        Assessing nest building in mice.
        Nat Protoc. 2006; 1: 1117-1119
        • Deacon R.M.
        • Rawlins J.N.
        T-maze alternation in the rodent.
        Nat Protoc. 2006; 1: 7-12
        • Ehrlichman R.S.
        • Gandal M.J.
        • Maxwell C.R.
        • Lazarewicz M.T.
        • Finkel L.H.
        • Contreras D.
        • et al.
        N-methyl-D-aspartic acid receptor antagonist-induced frequency oscillations in mice recreate pattern of electrophysiological deficits in schizophrenia.
        Neuroscience. 2009; 158: 705-712
        • Gandal M.J.
        • Ehrlichman R.S.
        • Rudnick N.D.
        • Siegel S.J.
        A novel electrophysiological model of chemotherapy-induced cognitive impairments in mice.
        Neuroscience. 2008; 157: 95-104
        • Lazarewicz M.T.
        • Ehrlichman R.S.
        • Maxwell C.R.
        • Gandal M.J.
        • Finkel L.H.
        • Siegel S.J.
        Ketamine modulates theta and gamma oscillations.
        J Cogn Neurosci. 2010; 22: 1452-1464
        • Connolly P.M.
        • Maxwell C.
        • Liang Y.
        • Kahn J.B.
        • Kanes S.J.
        • Abel T.
        • et al.
        The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components.
        Neurochem Res. 2004; 29: 1179-1188
        • Connolly P.M.
        • Maxwell C.R.
        • Kanes S.J.
        • Abel T.
        • Liang Y.
        • Tokarczyk J.
        • et al.
        Inhibition of auditory evoked potentials and prepulse inhibition of startle in DBA/2J and DBA/2Hsd inbred mouse substrains.
        Brain Res. 2003; 992: 85-95
        • Siegel S.J.
        • Connolly P.
        • Liang Y.
        • Lenox R.H.
        • Gur R.E.
        • Bilker W.B.
        • et al.
        Effects of strain, novelty, and NMDA blockade on auditory-evoked potentials in mice.
        Neuropsychopharmacology. 2003; 28: 675-682
        • Gandal M.J.
        • Edgar J.C.
        • Ehrlichman R.S.
        • Mehta M.
        • Roberts T.P.
        • Siegel S.J.
        Validating gamma oscillations and delayed auditory responses as translational biomarkers of autism.
        Biol Psychiatry. 2010; 68: 1100-1106
        • Arnold S.E.
        • Hyman B.T.
        • Van Hoesen G.W.
        • Damasio A.R.
        Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia.
        Arch Gen Psychiatry. 1991; 48: 625-632
        • Arnold S.E.
        • Ruscheinsky D.D.
        • Han L.Y.
        Further evidence of abnormal cytoarchitecture of the entorhinal cortex in schizophrenia using spatial point pattern analyses.
        Biol Psychiatry. 1997; 42: 639-647
        • Hahn C.G.
        • Wang H.Y.
        • Cho D.S.
        • Talbot K.
        • Gur R.E.
        • Berrettini W.H.
        • et al.
        Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia.
        Nat Med. 2006; 12: 824-828
        • Feng R.
        • Wang H.
        • Wang J.
        • Shrom D.
        • Zeng X.
        • Tsien J.Z.
        Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer’s presenilin-1 and presenilin-2.
        Proc Natl Acad Sci U S America. 2004; 101: 8162-8167
        • Ferguson C.
        • Hardy S.L.
        • Werner D.F.
        • Hileman S.M.
        • Delorey T.M.
        • Homanics G.E.
        New insight into the role of the beta3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout.
        BMC Neurosci. 2007; 8: 85
        • Kiselycznyk C.
        • Svenningsson P.
        • Delpire E.
        • Holmes A.
        Genetic, pharmacological and lesion analyses reveal a selective role for corticohippocampal GLUN2B in a novel repeated swim stress paradigm.
        Neuroscience. 2011; 193: 259-268
        • Mirnics K.
        • Norstrom E.M.
        • Garbett K.
        • Choi S.H.
        • Zhang X.
        • Ebert P.
        • Sisodia S.S.
        Molecular signatures of neurodegeneration in the cortex of PS1/PS2 double knockout mice.
        Mol Neurodegener. 2008; 3: 14
        • Sato C.
        • Turkoz M.
        • Dearborn J.T.
        • Wozniak D.F.
        • Kopan R.
        • Hass M.R.
        Loss of RBPj in postnatal excitatory neurons does not cause neurodegeneration or memory impairments in aged mice.
        PloS One. 2012; 7: e48180
        • Valor L.M.
        • Pulopulos M.M.
        • Jimenez-Minchan M.
        • Olivares R.
        • Lutz B.
        • Barco A.
        Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability.
        J Neurosci. 2011; 31: 1652-1663
        • Kellendonk C.
        Modeling excess striatal D2 receptors in mice.
        Prog Brain Res. 2009; 179: 59-65
        • Kellendonk C.
        • Simpson E.H.
        • Polan H.J.
        • Malleret G.
        • Vronskaya S.
        • Winiger V.
        • et al.
        Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning.
        Neuron. 2006; 49: 603-615
        • Krishnan G.P.
        • Vohs J.L.
        • Hetrick W.P.
        • Carroll C.A.
        • Shekhar A.
        • Bockbrader M.A.
        • O’Donnell B.F.
        Steady state visual evoked potential abnormalities in schizophrenia.
        Clin Neurophysiol. 2005; 116: 614-624
        • Winterer G.
        • Ziller M.
        • Dorn H.
        • Frick K.
        • Mulert C.
        • Wuebben Y.
        • et al.
        Schizophrenia: Reduced signal-to-noise ratio and impaired phase-locking during information processing.
        Clin Neurophysiol. 2000; 111: 837-849
        • Burnet P.W.
        • Eastwood S.L.
        • Harrison P.J.
        5-HT1A and 5-HT2A receptor mRNAs and binding site densities are differentially altered in schizophrenia.
        Neuropsychopharmacology. 1996; 15: 442-455
        • Knable M.B.
        • Barci B.M.
        • Bartko J.J.
        • Webster M.J.
        • Torrey E.F.
        Molecular abnormalities in the major psychiatric illnesses: Classification and Regression Tree (CRT) analysis of post-mortem prefrontal markers.
        Mol Psychiatry. 2002; 7: 392-404
        • Seeman P.
        • Bzowej N.H.
        • Guan H.C.
        • Bergeron C.
        • Reynolds G.P.
        • Bird E.D.
        • et al.
        Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer’s, Parkinson’s, and Huntington’s diseases.
        Neuropsychopharmacology. 1987; 1: 5-15
        • Suhara T.
        • Okubo Y.
        • Yasuno F.
        • Sudo Y.
        • Inoue M.
        • Ichimiya T.
        • et al.
        Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia.
        Arch Gen Psychiatry. 2002; 59: 25-30
        • Tuppurainen H.
        • Kuikka J.
        • Viinamaki H.
        • Husso-Saastamoinen M.
        • Bergstrom K.
        • Tiihonen J.
        Extrastriatal dopamine D 2/3 receptor density and distribution in drug-naive schizophrenic patients.
        Mol Psychiatry. 2003; 8: 453-455
        • Howes O.D.
        • Kapur S.
        The dopamine hypothesis of schizophrenia: Version III--the final common pathway.
        Schizophr Bull. 2009; 35: 549-562
        • Takahashi H.
        • Higuchi M.
        • Suhara T.
        The role of extrastriatal dopamine D2 receptors in schizophrenia.
        Biol Psychiatry. 2006; 59: 919-928
        • Chung H.J.
        • Ge W.P.
        • Qian X.
        • Wiser O.
        • Jan Y.N.
        • Jan L.Y.
        G protein-activated inwardly rectifying potassium channels mediate depotentiation of long-term potentiation.
        Proc Natl Acad Sci U S A. 2009; 106: 635-640
        • Chung H.J.
        • Qian X.
        • Ehlers M.
        • Jan Y.N.
        • Jan L.Y.
        Neuronal activity regulates phosphorylation-dependent surface delivery of G protein-activated inwardly rectifying potassium channels.
        Proc Natl Acad Sci U S A. 2009; 106: 629-634
        • Labouebe G.
        • Lomazzi M.
        • Cruz H.G.
        • Creton C.
        • Lujan R.
        • Li M.
        • et al.
        RGS2 modulates coupling between GABAB receptors and GIRK channels in dopamine neurons of the ventral tegmental area.
        Nat Neurosci. 2007; 10: 1559-1568
        • Padgett C.L.
        • Slesinger P.A.
        GABAB receptor coupling to G-proteins and ion channels.
        Adv Pharmacol. 2010; 58: 123-147
        • Xie K.
        • Allen K.L.
        • Kourrich S.
        • Colon-Saez J.
        • Thomas M.J.
        • Wickman K.
        • Martemyanov K.A.
        Gbeta5 recruits R7 RGS proteins to GIRK channels to regulate the timing of neuronal inhibitory signaling.
        Nat Neurosci. 2010; 13: 661-663
        • Beneyto M.
        • Meador-Woodruff J.H.
        Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia.
        Synapse. 2006; 60: 585-598
        • Breese C.R.
        • Freedman R.
        • Leonard S.S.
        Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers.
        Brain Res. 1995; 674: 82-90
        • Corti C.
        • Xuereb J.H.
        • Crepaldi L.
        • Corsi M.
        • Michielin F.
        • Ferraguti F.
        Altered levels of glutamatergic receptors and Na+/K+ ATPase-alpha1 in the prefrontal cortex of subjects with schizophrenia.
        Schizophr Res. 2011; 128: 7-14
        • Eastwood S.L.
        • McDonald B.
        • Burnet P.W.
        • Beckwith J.P.
        • Kerwin R.W.
        • Harrison P.J.
        Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia.
        Brain Res Mol Brain Res. 1995; 29: 211-223
        • Dracheva S.
        • McGurk S.R.
        • Haroutunian V.
        mRNA expression of AMPA receptors and AMPA receptor binding proteins in the cerebral cortex of elderly schizophrenics.
        J Neurosci Res. 2005; 79: 868-878
        • Lu W.
        • Gray J.A.
        • Granger A.J.
        • During M.J.
        • Nicoll R.A.
        Potentiation of synaptic AMPA receptors induced by the deletion of NMDA receptors requires the GluA2 subunit.
        J Neurophysiol. 2011; 105: 923-928
        • 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: 2921-2927
        • Curley A.A.
        • Arion D.
        • Volk D.W.
        • Asafu-Adjei J.K.
        • Sampson A.R.
        • Fish K.N.
        • Lewis D.A.
        Cortical deficits of glutamic acid decarboxylase 67 expression in schizophrenia: Clinical, protein, and cell type-specific features.
        Am J Psychiatry. 2011; 168: 921-929
        • Duncan C.E.
        • Webster M.J.
        • Rothmond D.A.
        • Bahn S.
        • Elashoff M.
        • Shannon Weickert C.
        Prefrontal GABA(A) receptor alpha-subunit expression in normal postnatal human development and schizophrenia.
        J Psychiatr Res. 2010; 44: 673-681
        • Torrey E.F.
        • Barci B.M.
        • Webster M.J.
        • Bartko J.J.
        • Meador-Woodruff J.H.
        • Knable M.B.
        Neurochemical markers for schizophrenia, bipolar disorder, and major depression in postmortem brains.
        Biol Psychiatry. 2005; 57: 252-260
        • Volk D.W.
        • Matsubara T.
        • Li S.
        • Sengupta E.J.
        • Georgiev D.
        • Minabe Y.
        • et al.
        Deficits in transcriptional regulators of cortical parvalbumin neurons in schizophrenia.
        Am J Psychiatry. 2012; 169: 1082-1091
        • Woo T.U.
        • Kim A.M.
        • Viscidi E.
        Disease-specific alterations in glutamatergic neurotransmission on inhibitory interneurons in the prefrontal cortex in schizophrenia.
        Brain Res. 2008; 1218: 267-277
        • Konradi C.
        • Yang C.K.
        • Zimmerman E.I.
        • Lohmann K.M.
        • Gresch P.
        • Pantazopoulos H.
        • et al.
        Hippocampal interneurons are abnormal in schizophrenia.
        Schizophr Res. 2011; 131: 165-173
        • Belforte J.E.
        • Zsiros V.
        • Sklar E.R.
        • Jiang Z.
        • Yu G.
        • Li Y.
        • et al.
        Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes.
        Nat Neurosci. 2010; 13: 76-83
        • Fung S.J.
        • Webster M.J.
        • Sivagnanasundaram S.
        • Duncan C.
        • Elashoff M.
        • Weickert C.S.
        Expression of interneuron markers in the dorsolateral prefrontal cortex of the developing human and in schizophrenia.
        Am J Psychiatry. 2010; 167: 1479-1488
        • Klausberger T.
        • Marton L.F.
        • O’Neill J.
        • Huck J.H.
        • Dalezios Y.
        • Fuentealba P.
        • et al.
        Complementary roles of cholecystokinin- and parvalbumin-expressing GABAergic neurons in hippocampal network oscillations.
        J Neurosci. 2005; 25: 9782-9793
        • Klausberger T.
        • Somogyi P.
        Neuronal diversity and temporal dynamics: The unity of hippocampal circuit operations.
        Science. 2008; 321: 53-57
        • Basar-Eroglu C.
        • Schmiedt-Fehr C.
        • Marbach S.
        • Brand A.
        • Mathes B.
        Altered oscillatory alpha and theta networks in schizophrenia.
        Brain Res. 2008; 1235: 143-152
        • Bates A.T.
        • Kiehl K.A.
        • Laurens K.R.
        • Liddle P.F.
        Low-frequency EEG oscillations associated with information processing in schizophrenia.
        Schizophr Res. 2009; 115: 222-230
        • Doege K.
        • Bates A.T.
        • White T.P.
        • Das D.
        • Boks M.P.
        • Liddle P.F.
        Reduced event-related low frequency EEG activity in schizophrenia during an auditory oddball task.
        Psychophysiology. 2009; 46: 566-577
        • Donkers F.C.
        • Schwikert S.R.
        • Evans A.M.
        • Cleary K.M.
        • Perkins D.O.
        • Belger A.
        Impaired neural synchrony in the theta frequency range in adolescents at familial risk for schizophrenia.
        Front Psychiatry. 2011; 2: 51
        • Hong L.E.
        • Summerfelt A.
        • Mitchell B.D.
        • O’Donnell P.
        • Thaker G.K.
        A shared low-frequency oscillatory rhythm abnormality in resting and sensory gating in schizophrenia.
        Clin Neurophysiol. 2012; 123: 285-292
        • Kittelberger K.
        • Hur E.E.
        • 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
        • Schmiedt C.
        • Brand A.
        • Hildebrandt H.
        • Basar-Eroglu C.
        Event-related theta oscillations during working memory tasks in patients with schizophrenia and healthy controls.
        Brain Res Cogn Brain Res. 2005; 25: 936-947
        • Westphal K.P.
        • Grozinger B.
        • Diekmann V.
        • Scherb W.
        • Reess J.
        • Leibing U.
        • Kornhuber H.H.
        Slower theta activity over the midfrontal cortex in schizophrenic patients.
        Acta Psychiatr Scand. 1990; 81: 132-138
        • Dickerson D.D.
        • Wolff A.R.
        • Bilkey D.K.
        Abnormal long-range neural synchrony in a maternal immune activation animal model of schizophrenia.
        J Neurosci. 2010; 30: 12424-12431
        • Neymotin S.A.
        • Lazarewicz M.T.
        • Sherif M.
        • Contreras D.
        • Finkel L.H.
        • Lytton W.W.
        Ketamine disrupts theta modulation of gamma in a computer model of hippocampus.
        J Neurosci. 2011; 31: 11733-11743
        • Wolf J.A.
        • Moyer J.T.
        • Lazarewicz M.T.
        • Contreras D.
        • Benoit-Marand M.
        • O’Donnell P.
        • Finkel L.H.
        NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron.
        J Neurosci. 2005; 25: 9080-9095
        • Greene J.R.
        • Mason A.
        Neuronal diversity in the subiculum: Correlations with the effects of somatostatin on intrinsic properties and on GABA-mediated IPSPs in vitro.
        J Neurophysiol. 1996; 76: 1657-1666
        • Greene J.R.
        • Mason A.
        Effects of somatostatin and related peptides on the membrane potential and input resistance of rat ventral subicular neurons, in vitro.
        J Pharmacol Exp Ther. 1996; 276: 426-432
        • Schweitzer P.
        • Madamba S.G.
        • Siggins G.R.
        Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons.
        J Neurophysiol. 1998; 79: 1230-1238
        • Morris H.M.
        • Hashimoto T.
        • Lewis D.A.
        Alterations in somatostatin mRNA expression in the dorsolateral prefrontal cortex of subjects with schizophrenia or schizoaffective disorder.
        Cereb Cortex. 2008; 18: 1575-1587
        • Roach B.J.
        • Mathalon D.H.
        Event-related EEG time-frequency analysis: An overview of measures and an analysis of early gamma band phase locking in schizophrenia.
        Schizophr Bull. 2008; 34: 907-926

      Linked Article