Skip to main content
    • Aa
    • Aa

Disruption of thalamocortical activity in schizophrenia models: relevance to antipsychotic drug action

  • Pau Celada (a1) (a2) (a3), Laia Lladó-Pelfort (a1) (a2) (a3), N. Santana (a1) (a2) (a3), L. Kargieman (a1) (a2) (a3), Eva Troyano-Rodriguez (a1) (a2) (a3), M. S. Riga (a1) (a2) (a3) and Francesc Artigas (a1) (a2) (a3)
  • DOI:
  • Published online: 01 July 2013

Non-competitive NMDA receptor antagonists are widely used as pharmacological models of schizophrenia due to their ability to evoke the symptoms of the illness. Likewise, serotonergic hallucinogens, acting on 5-HT2A receptors, induce perceptual and behavioural alterations possibly related to psychotic symptoms. The neurobiological basis of these alterations is not fully elucidated. Data obtained in recent years revealed that the NMDA receptor antagonist phencyclidine (PCP) and the serotonergic hallucinogen 1-(2,5-dimethoxy-4-iodophenyl-2-aminopropane; DOI) produce a series of common actions in rodent prefrontal cortex (PFC) that may underlie psychotomimetic effects. Hence, both agents markedly disrupt PFC function by altering pyramidal neuron discharge (with an overall increase) and reducing the power of low frequency cortical oscillations (LFCO; < 4 Hz). In parallel, PCP increased c-fos expression in excitatory neurons of various cortical areas, the thalamus and other subcortical structures, such as the amygdala. Electrophysiological studies revealed that PCP altered similarly the function of the centromedial and mediodorsal nuclei of the thalamus, reciprocally connected with PFC, suggesting that its psychotomimetic properties are mediated by an alteration of thalamocortical activity (the effect of DOI was not examined in the thalamus). Interestingly, the observed effects were prevented or reversed by the antipsychotic drugs clozapine and haloperidol, supporting that the disruption of PFC activity is intimately related to the psychotomimetic activity of these agents. Overall, the present experimental model can be successfully used to elucidate the neurobiological basis of schizophrenia symptoms and to examine the potential antipsychotic activity of new drugs in development.

Corresponding author
Address for correspondence: Dr F. Artigas, Department of Neurochemistry and Neuropharmacology, IIBB-CSIC (IDIBAPS), Rosselló, 161, 6th floor, 08036 Barcelona, Spain. Tel.:+3493 363 8315Fax:+3493 363
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

A Ahnaou , S Nayak , A Heylen , D Ashton , WHIM Drinkenburg (2007) Sleep and EEG profile in neonatal hippocampal lesion model of schizophrenia. Physiol Behav 92:461467.

M Amargos-Bosch , A Bortolozzi , MV Puig , J Serrats , A Adell , P Celada , M Toth , G Mengod , F Artigas (2004) Co-expression and in vivo interaction of serotonin(1A) and serotonin(2A) receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex 14:281299.

M Amargos-Bosch , X Lopez-Gil , F Artigas , A Adell (2006) Clozapine and olanzapine, but not haloperidol, suppress serotonin efflux in the medial prefrontal cortex elicited by phencyclidine and ketamine. Int J Neuropsychopharm 9:565573.

H Anver , PD Ward , A Magony , M Vreugdenhil (2011) NMDA Receptor hypofunction phase couples independent gamma-oscillations in the rat visual cortex. Neuropsychopharmacology 36:519528.

F Artigas (2010) The prefrontal cortex: a target for antipsychotic drugs. Acta Psychiatr Scand 121:1121.

G Aston-Jones , JD Cohen (2005) An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annu Rev Neurosci 28:403450.

E Basar , B Guntekin (2008) A review of brain oscillations in cognitive disorders and the role of neurotransmitters. Brain Res 1235:172193.

AT Bates , KA Kiehl , KR Laurens , PF Liddle (2009) Low-frequency EEG oscillations associated with information processing in schizophrenia. Schizophr Res 115:222230.

D Begic , L Hotujac , N Jokic-Begic (2000) Quantitative EEG in ‘positive’ and ‘negative’ schizophrenia. Acta Psychiatr Scand 101:307311.

JE Belforte , V Zsiros , ER Sklar , ZH Jiang , G Yu , YQ Li , EM Quinlan , K Nakazawa (2010) Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 13:76–U240.

HW Berendse , HJ Groenewegen (1991) Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat. Neuroscience 42:73102.

H Berger (1929) Electroencephalogram in humans. Archiv fur Psychiatrie und Nervenkrankheiten 87:527570.

R Bodizs , M Bekesy , A Szucs , P Barsi , P Halasz (2002) Sleep-dependent hippocampal slow activity correlates with waking memory performance in humans. Neurobiol Learn Mem 78:441457.

A Bortolozzi , M Masana , L Diaz-Mataix , R Cortes , MC Scorza , JA Gingrich , M Toth , F Artigas (2010) Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT(1A) receptors but not 5-HT(2A) receptors. Int J Neuropsychopharmacol 13:12991314.

J Camchong , AW MacDonald , C Bell , BA Mueller , KO Lim (2011) Altered functional and anatomical connectivity in schizophrenia. Schizophr Bull 37:640650.

RN Cardinal , JA Parkinson , J Hall , BJ Everitt (2002) Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 26:321352.

M Carlen , K Meletis , JH Siegle , JA Cardin , K Futai , D Vierling-Claassen , C Ruhlmann , SR Jones , K Deisseroth , M Sheng , CI Moore , LH Tsai (2012) A critical role for NMDA receptors in parvalbumin interneurons for gamma rhythm induction and behavior. Mol Psychiatry 17:537548.

GC Carlson , K Talbot , TB Halene , MJ Gandal , HA Kazi , L Schlosser , QH Phung , RE Gur , SE Arnold , SJ Siegel (2011) Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia. Proc Natl Acad Sci USA 108:E962E970.

M Carlsson , A Carlsson (1989) Dramatic synergism between MK-801 and clonidine with respect to locomotor stimulatory effect in monoamine-depleted mice. J Neural Transm 77:6571.

NA Cavara , M Hollmann (2008) Shuffling the deck anew: how NR3 tweaks NMDA receptor function. Mol Neurobiol 38:1626.

P Celada , F Artigas (2007) Serotonin modulation of cortical activity. In: Monoaminergic modulation of cortical excitability (KY Tseng , M Atzori , ed), pp6789. New York: Springer Science+Business Media, LLC.

P Celada , MV Puig , L Diaz-Mataix , F Artigas (2008) The hallucinogen DOI reduces low-frequency oscillations in rat prefrontal cortex: reversal by antipsychotic drugs. Biol Psychiatry 64:392400.

SM Clinton , JH Meador-Woodruff (2004) Thalamic dysfunction in schizophrenia: neurochemical, neuropathological, and in vivo imaging abnormalities. Schizophr Res 69:237253.

V Crunelli , SW Hughes (2010) The slow (<1 Hz) rhythm of non-REM sleep: a dialogue between three cardinal oscillators. Nat Neurosci 13:1018.

RJ Davidson , W Irwin (1999) The functional neuroanatomy of emotion and affective style. Trends Cogn Sci 3:1121.

J de Almeida , G Mengod (2007) Quantitative analysis of glutamatergic and GABAergic neurons expressing 5-HT2A receptors in human and monkey prefrontal cortex. J Neurochem 103:475486.

J de Almeida , G Mengod (2008) Serotonin 1A receptors in human and monkey prefrontal cortex are mainly expressed in pyramidal neurons and in a GABAergic interneuron subpopulation: implications for schizophrenia and its treatment. J Neurochem 107:488496.

J Defelipe , SHC Hendry , EG Jones (1989) Visualization of chandelier cell axons by parvalbumin immunoreactivity in monkey cerebral-cortex. Proc Natl Acad Sci USA 86:20932097.

J Defelipe (2013) New insights into the classification and nomenclature of cortical GABAergic interneurons. Nat Rev Neurosci 14:202216.

O Devinsky , MJ Morrell , BA Vogt (1995) Contributions of anterior cingulate cortex to behaviour. Brain 118(Pt 1):279306.

L Diaz-Mataix , MC Scorza , A Bortolozzi , M Toth , P Celada , F Artigas (2005) Involvement of 5-HT1A receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action. J Neurosci 25:1083110843.

K Dzirasa , AJ Ramsey , DY Takahashi , J Stapleton , JM Potes , JK Williams , RR Gainetdinov , K Sameshima , MG Caron , MAL Nicolelis (2009) Hyperdopaminergia and NMDA receptor hypofunction disrupt neural phase signaling. J Neurosci 29:82158224.

AK Engel , W Singer (2001) Temporal binding and the neural correlates of sensory awareness. Trends Cogn Sci 5:1625.

A Fisahn , J Neddens , LQ Yan , A Buonanno (2009) Neuregulin-1 modulates hippocampal gamma oscillations: implications for schizophrenia. Cereb Cortex 19:612618.

JM Fuster (2001) The prefrontal cortex – an update: time is of the essence. Neuron 30:319333.

JM Fuster (2008) The prefrontal cortex, 4th edn. Los Angeles, California, USA: Academic Press.

PL Gabbott , TA Warner , PR Jays , P Salway , SJ Busby (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492:145177.

M Galarreta , S Hestrin (2001) Electrical synapses between GABA-releasing interneurons. Nat Rev Neurosci 2:425433.

MA Geyer , K Krebs-Thomson , DL Braff , NR Swerdlow (2001) Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 156:117154.

Y Goto , AA Grace (2006) Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development. Biol Psychiatry 60:12591267.

HJ Groenewegen , HB Uylings (2000) The prefrontal cortex and the integration of sensory, limbic and autonomic information. Prog Brain Res 126:328.

M Hajos , WE Hoffmann , B Kocsis (2008) Activation of cannabinoid-1 receptors disrupts sensory gating and neuronal oscillation: relevance to schizophrenia. Biol Psychiatry 63:10751083.

PJ Harrison (1999) The neuropathological effects of antipsychotic drugs. Schizophr Res 40:8799.

PJ Harrison , DR Weinberger (2005) Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 10:4068.

XL Hill , MC Scorza (2012) Role of the anterior thalamic nucleus in the motor hyperactivity induced by systemic MK-801 administration in rats. Neuropharmacology 62:24402446.

RE Hoffman , TH Mcglashan (1993) Neurodynamics and schizophrenia research – editors introduction. Schizophr Bull 19:1519.

H Homayoun , B Moghaddam (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27:1149611500.

LE Hong , A Summerfelt , RW Buchanan , P O'Donnell , GK Thaker , MA Weiler , AC Lahti (2010) Gamma and delta neural oscillations and association with clinical symptoms under subanesthetic ketamine. Neuropsychopharmacology 35:632640.

C Hull , JS Isaacson , M Scanziani (2009) Postsynaptic mechanisms govern the differential excitation of cortical neurons by thalamic inputs. J Neurosci 29:91279136.

MJ Hunt , M Falinska , S Leski , DK Wojcik , S Kasicki (2011) Differential effects produced by ketamine on oscillatory activity recorded in the rat hippocampus, dorsal striatum and nucleus accumbens. J Psychopharmacol 25:808821.

J Ichikawa , H Ishii , S Bonaccorso , WL Fowler , IA O'Laughlin , HY Meltzer (2001) 5-HT2A and D-2 receptor blockade increases cortical DA release via 5-HT1A receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release. J Neurochem 76:15211531.

T Itoh , T Sumiyoshi , Y Higuchi , M Suzuki , Y Kawasaki (2011) LORETA analysis of three-dimensional distribution of delta band activity in schizophrenia: relation to negative symptoms. Neurosci Res 70:442448.

ME Jackson , H Homayoun , B Moghaddam (2004) NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex. Proc Natl Acad Sci USA 101:84678472.

E Jodo , Y Suzuki , T Katayama , KY Hoshino , S Takeuchi , SI Niwa , Y Kayama (2005) Activation of medial prefrontal cortex by phencyclidine is mediated via a hippocampo-prefrontal pathway. Cereb Cortex 15:663669.

EG Jones (1997) Cortical development and thalamic pathology in schizophrenia. Schizophr Bull 23:483501.

EG Jones (2002) Thalamic circuitry and thalamocortical synchrony. Philos Trans R Soc Lond B Biol Sci 357:16591673.

I Karavanova , K Vasudevan , J Cheng , A Buonanno (2007) Novel regional and developmental NMDA receptor expression patterns uncovered in NR2C subunit-beta-galactosidase knock-in mice. Mol Cell Neurosci 34:468480.

L Kargieman , N Santana , G Mengod , P Celada , F Artigas (2007) Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine. Proc Natl Acad Sci USA 104:1484314848.

L Kargieman , MS Riga , F Artigas , P Celada (2012) Clozapine reverses phencyclidine-induced desynchronization of prefrontal cortex through a 5-HT1A receptor-dependent mechanism. Neuropsychopharmacology 37:723733.

MS Keshavan , CF Reynolds , JM Miewald , DM Montrose , JA Sweeney , RC Vasko , DJ Kupfer (1998) Delta sleep deficits in schizophrenia – evidence from automated analyses of sleep data. Arch Gen Psychiatry 55:443448.

M Kikuchi , T Hashimoto , T Nagasawa , T Hirosawa , Y Minabe , M Yoshimura , W Strik , T Dierks , T Koenig (2011) Frontal areas contribute to reduced global coordination of resting-state gamma activities in drug-naive patients with schizophrenia. Schizophr Res 130:187194.

T Kiss , WE Hoffmann , M Hajos (2011a) Delta oscillation and short-term plasticity in the rat medial prefrontal cortex: modelling NMDA hypofunction of schizophrenia. Int J Neuropsychopharm 14:2942.

T Kiss , WE Hoffmann , L Scott , TT Kawabe , AJ Milici , EA Nilsen , M Hajos (2011b) Role of thalamic projection in NMDA receptor-induced disruption of cortical slow oscillation and short-term plasticity. Front Psychiatry 2:14.

K Kittelberger , EE Hur , S Sazegar , V Keshavan , B Kocsis (2012) 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 217:395409.

B Kocsis (2012) Differential role of NR2A and NR2B subunits in N-methyl-d-aspartate receptor antagonist-induced aberrant cortical gamma oscillations. Biol Psychiatry 71:987995.

C Konradi , S Heckers (2003) Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol Ther 97:153179.

T Korotkova , EC Fuchs , A Ponomarenko , J von Engelhardt , H Monyer (2010) NMDA receptor ablation on parvalbumin-positive interneurons impairs hippocampal synchrony, spatial representations, and working memory. Neuron 68:557569.

JH Krystal , DC D'Souza , D Mathalon , E Perry , A Belger , R Hoffman (2003) NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology (Berl) 169:215233.

M Kuroda , J Yokofujita , K Murakami (1998) An ultrastructural study of the neural circuit between the prefrontal cortex and the mediodorsal nucleus of the thalamus. Prog Neurobiol 54:417458.

CG Lau , RS Zukin (2007) NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. Nat Rev Neurosci 8:413426.

MT Lazarewicz , RS Ehrlichman , CR Maxwell , MJ Gandal , LH Finkel , SJ Siegel (2010) Ketamine modulates theta and gamma oscillations. J Cogn Neurosci 22:14521464.

N Leresche , D Jassikgerschenfeld , M Haby , I Soltesz , V Crunelli (1990) Pacemaker-like and other types of spontaneous membrane-potential oscillations of thalamocortical cells. Neurosci Lett 113:7277.

DA Lewis , G Gonzalez-Burgos (2006) Pathophysiologically based treatment interventions in schizophrenia. Nat Med 12:10161022.

DA Lewis , JA Lieberman (2000) Catching up on schizophrenia: natural history and neurobiology. Neuron 28:325334.

DA Lewis , T Hashimoto , DW Volk (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6:312324.

DA Lewis , AA Curley , JR Glausier , DW Volk (2012) Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends Neurosci 35:5767.

JE Lisman , HJ Pi , YC Zhang , NA Otmakhova (2010) A thalamo-hippocampal-ventral tegmental area loop may produce the positive feedback that underlies the psychotic break in schizophrenia. Biol Psychiatry 68:1724.

RR Llinas , M Steriade (2006) Bursting of thalamic neurons and states of vigilance. J Neurophysiol 95:32973308.

DJ Lodge , MM Behrens , AA Grace (2009) A loss of parvalbumin-containing interneurons is associated with diminished oscillatory activity in an animal model of schizophrenia. J Neurosci 29:23442354.

X Lopez-Gil , Z Babot , M Amargos-Bosch , C Sunol , F Artigas , A Adell (2007) Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology 32:20872097.

JY Ma , LS Leung (2007) The supramammillo-septal-hippocampal pathway mediates sensorimotor gating impairment and hyperlocomotion induced by MK-801 and ketamine in rats. Psychopharmacology 191:961974.

L Marshall , H Helgadottir , M Molle , J Born (2006) Boosting slow oscillations during sleep potentiates memory. Nature 444:610613.

DA Mccormick , HC Pape (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J Physiol-London 431:291318.

HY Meltzer (1999) The role of serotonin in antipsychotic drug action. Neuropsychopharmacology 21:106S115S.

EK Miller , JD Cohen (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24:167202.

H Monyer , N Burnashev , DJ Laurie , B Sakmann , PH Seeburg (1994) Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 12:529540.

DE Nichols (2004) Hallucinogens. Pharmacol Ther 101:131181.

CM Niswender , PJ Conn (2010) Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 50:295322.

PL Nunez , R Srinivasan (2006) A theoretical basis for standing and traveling brain waves measured with human EEG with implications for an integrated consciousness. Clin Neurophysiol 117:24242435.

P Paoletti , J Neyton (2007) NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 7:3947.

H Petsche , H Pockberger , P Rappelsberger (1984) On the search for the sources of the electroencephalogram. Neuroscience 11:127.

KG Phillips , MC Cotel , AP McCarthy , DM Edgar , M Tricklebank , MJ O'Neill , MW Jones , KA Wafford (2012) Differential effects of NMDA antagonists on high frequency and gamma EEG oscillations in a neurodevelopmental model of schizophrenia. Neuropharmacology 62:13591370.

ML Phillips , WC Drevets , SL Rauch , R Lane (2003) Neurobiology of emotion perception I: the neural basis of normal emotion perception. Biol Psychiatry 54:504514.

D Pinault (2008) N-methyl d-aspartate receptor antagonists ketarnine and MK-801 induce wake-related aberrant, gamma oscillations in the rat neocortex. Biol Psychiatry 63:730735.

J Poulin , E Stip , R Godbout (2008) REM sleep EEG spectral analysis in patients with first-episode schizophrenia. J Psychiatr Res 42:10861093.

MV Puig , P Celada , L Diaz-Mataix , F Artigas (2003) In vivo modulation of the activity of pyramidal neurons in the rat medial prefrontal cortex by 5-HT2A receptors: relationship to thalamocortical afferents. Cereb Cortex 13:870882.

MV Puig , F Artigas , P Celada (2005) Modulation of the activity of pyramidal neurons in rat prefrontal cortex by raphe stimulation in vivo: involvement of serotonin and GABA. Cereb Cortex 15:114.

J Riba , P Anderer , A Morte , G Urbano , F Jane , B Saletu , MJ Barbanoj (2002) Topographic pharmaco-EEG mapping of the effects of the South American psychoactive beverage ayahuasca in healthy volunteers. Br J Clin Pharmacol 53:613628.

BS Rockstroh , C Wienbruch , WJ Ray , T Elbert (2007) Abnormal oscillatory brain dynamics in schizophrenia: a sign of deviant communication in neural network? BMC Psychiatry 7:44.

H Rollema , Y Lu , AW Schmidt , SH Zorn (1997) Clozapine increases dopamine release in prefrontal cortex by 5-H(1)A receptor activation. Eur J Pharmacol 338:R3R5.

N Santana , A Bortolozzi , J Serrats , G Mengod , F Artigas (2004) Expression of serotonin1A and serotonin2A receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex 14:11001109.

N Santana , G Mengod , F Artigas (2009) Quantitative analysis of the expression of dopamine D-1 and D-2 receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex 19:849860.

N Santana , E Troyano-Rodriguez , G Mengod , P Celada , F Artigas (2011) Activation of thalamocortical networks by the N-methyl-d-aspartate receptor antagonist phencyclidine: reversal by clozapine. Biol Psychiatry 69:918927.

JA Saunders , MJ Ganda , SJ Siegel (2012) NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia. Neurobiol Dis 46:93100.

R Schreiber , M Brocco , MJ Millan (1994) Blockade of the discriminative stimulus effects of DOI by MDL 100,907 and the ‘atypical’ antipsychotics, clozapine and risperidone. Eur J Pharmacol 264:99102.

RA Schug , YL Yang , A Raine , CB Han , JH Liu , LJ Li (2011) Resting EEG deficits in accused murderers with schizophrenia. Psychiatry Res-Neuroimaging 194:8594.

JK Seamans , CR Yang (2004) The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol 74:158.

C Sebban , B Tesolin-Decros , J Ciprian-Ollivier , L Perret , M Spedding (2002) Effects of phencyclidine (PCP) and MK 801 on the EEGq in the prefrontal cortex of conscious rats; antagonism by clozapine, and antagonists of AMPA-, alpha(1)- and 5-HT(2A)-receptors. Br J Pharmacol 135:6578.

M Sekimoto , M Kato , T Watanabe , N Kajimura , K Takahashi (2007) Reduced frontal asymmetry of delta waves during all-night sleep in schizophrenia. Schizophr Bull 33:13071311.

LD Selemon , PS Goldman-Rakic (1999) The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 45:1725.

SS Shergill , MJ Brammer , SC Williams , RM Murray , PK McGuire (2000) Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. Arch Gen Psychiatry 57:10331038.

S Shipp (2007) Structure and function of the cerebral cortex. Curr Biol 17:R443R449.

T Sigurdsson , KL Stark , M Karayiorgou , JA Gogos , JA Gordon (2010) Impaired hippocampal-prefrontal synchrony in a genetic mouse model of schizophrenia. Nature 464:763767.

LR Skelly , V Calhoun , SA Meda , J Kim , DH Mathalon , GD Pearlson (2008) Diffusion tensor imaging in schizophrenia: relationship to symptoms. Schizophr Res 98:157162.

KM Spencer (2012) Baseline gamma power during auditory steady-state stimulation in schizophrenia. Front Hum Neurosci 5:190.

HWM Steinbusch (1981) Distribution of serotonin-immunoreactivity in the central nervous-system of the rat – cell-bodies and terminals. Neuroscience 6:557618.

M Steriade (2001) The GABAergic reticular nucleus: a preferential target of corticothalamic projections. Proc Natl Acad Sci USA 98:36253627.

M Steriade (2006) Grouping of brain rhythms in corticothalamic systems. Neuroscience 137:10871106.

P Steullet , JH Cabungcal , A Kulak , R Kraftsik , Y Chen , TP Dalton , M Cuenod , KQ Do (2010) Redox dysregulation affects the ventral but not dorsal hippocampus: impairment of parvalbumin neurons, gamma oscillations, and related behaviors. J Neurosci 30:25472558.

QQ Sun , JR Huguenard , DA Prince (2006) Barrel cortex microcircuits: thalamocortical feedforward inhibition in spiny stellate cells is mediated by a small number of fast-spiking interneurons. J Neurosci 26:12191230.

Y Suzuki , E Jodo , S Takeuchi , S Niwa , Y Kayama (2002) Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats. Neuroscience 114:769779.

CJ Swanson , M Bures , MP Johnson , AM Linden , JA Monn , DD Schoepp (2005) Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 4:131144.

RD Traub , A Bibbig , A Fisahn , FEN Lebeau , MA Whittington , EH Buhl (2000) A model of gamma-frequency network oscillations induced in the rat CA3 region by carbachol in vitro. Eur J Neurosci 12:40934106.

KY Tseng , N Mallet , KL Toreson , C Le Moine , F Gonon , P O'Donnell (2006) Excitatory response of prefrontal cortical fast-spiking interneurons to ventral tegmental area stimulation in vivo. Synapse 59:412417.

A Valdes-Cruz , JV Negrete-Diaz , VM Magdaleno-Madrigal , D Martinez-Vargas , R Fernandez-Mas , S Almazan-Alvarado , ME Torres-Garcia , G Flores (2012) Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats. Synapse 66:738746.

CG Vaneden , EMD Hoorneman , RM Buijs , MAH Matthijssen , M Geffard , HBM Uylings (1987) Immunocytochemical localization of dopamine in the prefrontal cortex of the rat at the light and electron-microscopic level. Neuroscience 22:849862.

NC Venables , EM Bernat , SR Sponheim (2009) Genetic and disorder-specific aspects of resting state EEG abnormalities in schizophrenia. Schizophr Bull 35:826839.

Z Vukadinovic (2011) Sleep abnormalities in schizophrenia may suggest impaired trans-thalamic cortico-cortical communication: towards a dynamic model of the illness. Eur J Neurosci 34:10311039.

Z Vukadinovic , I Rosenzweig (2012) Abnormalities in thalamic neurophysiology in schizophrenia: could psychosis be a result of potassium channel dysfunction? Neurosci Biobehav Rev 36:960968.

L Watis , SH Chen , HC Chua , SA Chong , K Sim (2008) Glutamatergic abnormalities of the thalamus in schizophrenia: a systematic review. J Neural Transm 115:493511.

A Wenzel , JM Fritschy , H Mohler , D Benke (1997) NMDA receptor heterogeneity during postnatal development of the rat brain: differential expression of the NR2A, NR2B, and NR2C subunit proteins. J Neurochem 68:469478.

TUW Woo , AM Kim , E Viscidi (2008) Disease-specific alterations in glutamatergic neurotransmission on inhibitory interneurons in the prefrontal cortex in schizophrenia. Brain Res 1218:267277.

J Wood , Y Kim , B Moghaddam (2012) Disruption of prefrontal cortex large scale neuronal activity by different classes of psychotomimetic drugs. J Neurosci 32:30223031.

Y Zhang , MM Behrens , JE Lisman (2008) Prolonged exposure to NMDAR antagonist suppresses inhibitory synaptic transmission in prefrontal cortex. J Neurophysiol 100:959965.

Y Zhang , T Yoshida , DB Katz , JE Lisman (2012) NMDAR antagonist action in thalamus imposes delta oscillations on the hippocampus. J Neurophysiol 107:31813189.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *