Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP)

Javitt, Daniel C.; Jayachandra, Mahesh; Lindsley, Robert W.; Specht, Colleen M.; Schroeder, Charles E.

doi:10.1016/s1388-2457(99)00313-2

Cited by 74 publications

(68 citation statements)

References 19 publications

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“…Several lines of evidence indicate reduced NMDA receptor (NMDAR) signalling in schizophrenia (Moghaddam, 2003;Javitt and Zukin, 1991) and in particular in the pathophysiology of the observed startle habituation, gating, and AEP generation alterations in schizophrenia (Javitt et al, 2000a;Klamer et al, 2004;Geyer et al, 2001). To provide supporting evidence for this hypothesis we tested a mouse mutant with 90% reduced expression of the NR1 subunit of the NMDA receptor (subsequently named NR1 mutants in this paper) in these paradigms (Mohn et al, 1999).…”

Section: Introductionmentioning

confidence: 90%

“…Thus our findings differ from the peak recovery profile observed in patients with schizophrenia who show a deficit in generation of the maximum P1 and N1 at long ISIs, but no difference in the slope of the peak recovery function (Roth et al, 1980;Shelley et al, 1999). Our initial hypothesis to find a similar profile in the NR1 mutant mice was based on studies in rats, non-human primates and healthy volunteers, in which such a profile was reproduced by acute application of NMDAR antagonists, pointing to a possible involvement of the NMDAR in this deficit (Javitt et al, 2000a;Ehlers et al, 1992;Umbricht et al, 2004a). Furthermore, previous studies have shown that the mouse AEP peaks P1, N1, and P2 display refractory curves comparable to their putative human correlates (P1, N1, P2) (Umbricht et al, 2004b;Maxwell et al, 2004).…”

Section: Aep Peak Refractorinessmentioning

confidence: 98%

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Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Bickel

Lipp

Umbricht

2007

Neuropsychopharmacol

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Cognitive deficits in schizophrenia include impairments at automatic, preattentive stages of sensory information processing. These deficits are evident in the prepulse inhibition-(PPI) and habituation of the auditory startle response paradigm, the paired tone paradigm in the EEG, and the peak recovery function of auditory evoked potentials (AEP). Administration of NMDA receptor antagonists reliably disrupts PPI and habituation of the startle, but not gating of AEPs in rodents. In the peak recovery paradigm, patients with schizophrenia and primates treated with NMDA receptor antagonists show reduced maximal response at long interstimulus intervals (ISI), but normal responses at short ISIs. Thus reduced NMDA receptor signalling may underlie alterations in these paradigms observed in schizophrenia. We tested the paradigms mentioned in mouse mutants with reduced expression of the NR1 subunit of the NMDA receptor (N ¼ 15) and their wild-type littermates (N ¼ 16). The NR1 mutant mice showed impaired habituation and PPI of the auditory startle response, as well as impaired gating in the paired tone paradigm. Deficits between the two gating measures did not correlate, corroborating previous evidence that these paradigms measure distinct processes. In the peak recovery paradigm, the NR1 mutants showed increased responses of the AEPs P1 and N1 at short ISIs but no difference between groups were observed at long ISIs. In conclusion, the NR1 hypomorphic mice modelled sensory and sensorimotor gating and startle habituation deficits observed in schizophrenia, but failed to model alterations in the peak recovery function.

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Section: Introductionmentioning

confidence: 90%

Section: Aep Peak Refractorinessmentioning

confidence: 98%

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Bickel

Lipp

Umbricht

2007

Neuropsychopharmacol

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“…Two tasks that measure the sensory gating of event-related potentials (ERPs) are the paired click paradigm, as a transient gating measure, and the interstimulus interval paradigm (ISI), as a steady-state gating measure (Erwin et al, 1994). The paired click paradigm contains two tones presented 500 ms apart with a 9-s interval between pairs, while the ISI task typically utilizes trains of stimuli at short intervals ranging from 0.25 to 1 s and longer intervals ranging from 2 to 10 s. During the ISI task in human studies, the amplitude of the N100 decreases with decreasing interstimulus intervals in healthy individuals (Boutros et al, 1999;Javitt et al, 2000). In contrast to the N100, the amplitude of the human P50 does not increase with increasing interstimulus intervals ranging from 1 to 16 s (Javitt et al, 2000;McFarland et al, 1975;Onitsuka et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The paired click paradigm contains two tones presented 500 ms apart with a 9-s interval between pairs, while the ISI task typically utilizes trains of stimuli at short intervals ranging from 0.25 to 1 s and longer intervals ranging from 2 to 10 s. During the ISI task in human studies, the amplitude of the N100 decreases with decreasing interstimulus intervals in healthy individuals (Boutros et al, 1999;Javitt et al, 2000). In contrast to the N100, the amplitude of the human P50 does not increase with increasing interstimulus intervals ranging from 1 to 16 s (Javitt et al, 2000;McFarland et al, 1975;Onitsuka et al, 2000). While some reports suggest that the human P200 displays an increase in amplitude with increasing ISI, to our knowledge, the human P200 has not been thoroughly investigated using this paradigm (Budd et al, 1998;Shelley et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…The neurobiology of sensory processing deficits in schizophrenia has been investigated with auditory ERPs in monkeys, cats, rats, and mice, using tasks similar to those used in humans (Boutros et al, 1997;de Bruin et al, 1999;Javitt et al, 2000;Pincze et al, 2001;Siegel et al, 2003;Simosky et al, 2003;Stevens et al, 2001Stevens et al, , 1997. To interpret the findings in these studies, it is important to understand the relationship between auditory evoked components in the species being studied and the analogous components in human.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Chronic Olanzapine and Haloperidol Differ on the Mouse N1 Auditory Evoked Potential

Maxwell

Liang

Weightman

et al. 2004

Neuropsychopharmacol

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Auditory evoked potentials have been used in a variety of animal models to assess information-processing impairments in schizophrenia. Previous mouse models have primarily employed a paired click paradigm to assess the transient measures of auditory gating. The current study uses stimulus trains at varied interstimulus intervals (ISI) between 0.25 and 8 s in mice to assess the effects of chronic olanzapine and haloperidol on auditory processing. Data indicate that olanzapine increases the amplitude of the N40, P80, and P20/N40 components of the auditory evoked potential, whereas haloperidol had no such effect. The ISI paradigm also allowed for an evaluation of several components of the mouse evoked potential to assess those that display response properties similar to the human P50 and N100. Data suggest that the mouse N40 displays an ISI response relationship that shares characteristics with the human N100, whereas the P20 appears more consistent with the human P50 across the ISI range evaluated in this task. This study suggests that olanzapine may help improve N100 impairments seen in schizophrenia, while haloperidol does not.

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Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

Butler¹,

Zemon²,

Schechter³

et al. 2005

Arch Gen Psychiatry

346

289

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These findings confirm the existence of early-stage visual processing dysfunction in schizophrenia and provide the first evidence that such deficits are due to decreased nonlinear signal amplification, consistent with glutamatergic theories. Neuroimaging studies support the hypothesis of dysfunction within low-level visual pathways involving thalamocortical radiations. Deficits in early-stage visual processing significantly predict higher cognitive deficits.

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Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP)

Cited by 74 publications

References 19 publications

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Early Auditory Sensory Processing Deficits in Mouse Mutants with Reduced NMDA Receptor Function

Effects of Chronic Olanzapine and Haloperidol Differ on the Mouse N1 Auditory Evoked Potential

Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

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