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Impaired attentional modulation of auditory evoked potentials in N-methyl-D-aspartate NR1 hypomorphic mice


Bickel, S; Lipp, H P; Umbricht, D (2007). Impaired attentional modulation of auditory evoked potentials in N-methyl-D-aspartate NR1 hypomorphic mice. Genes, Brain and Behavior, 6(6):558-568.

Abstract

In human neurophysiology, auditory event-related potentials (AEPs) are used to investigate cognitive processes such as selective attention. Selective attention to specific tones causes a negative enhancement of AEPs known as processing negativity (PN), which is reduced in patients with schizophrenia. The evidence suggests that impaired selective attention in these patients may partially depend on deficient N-methyl-D-aspartate receptor (NMDAR)-mediated signaling. The goal of this study was to corroborate the involvement of the NMDAR in selective attention using a mouse model. To this end, we first investigated the presence of PN-like activity in C57BL/6J mice by recording AEPs during a fear-conditioning paradigm. Two alternating trains of tones, differing in stimulus duration, were presented on 7 subsequent days. One group received a mild foot shock delivered within the presentation of one train (conditioning train) on days 3-5 (conditioning days), while controls were never shocked. The fear-conditioned group (n= 9) indeed showed a PN-like activity during conditioning days manifested as a significant positive enhancement in the AEPs to the stimuli in the conditioning train that was not observed in the controls. The same paradigm was then applied to mice with reduced expression of the NMDAR1 (NR1) subunit and to a wild-type control group (each group n= 6). The NR1 mutants showed an associative AEP enhancement, but its magnitude was significantly reduced as compared with the magnitude in wild-type mice. We conclude that electrophysiological manifestations of selective attention are observable yet of different polarity in mice and that they require intact NMDAR-mediated signaling. Thus, deficient NMDAR functioning may contribute to abnormal selective attention in schizophrenia.

In human neurophysiology, auditory event-related potentials (AEPs) are used to investigate cognitive processes such as selective attention. Selective attention to specific tones causes a negative enhancement of AEPs known as processing negativity (PN), which is reduced in patients with schizophrenia. The evidence suggests that impaired selective attention in these patients may partially depend on deficient N-methyl-D-aspartate receptor (NMDAR)-mediated signaling. The goal of this study was to corroborate the involvement of the NMDAR in selective attention using a mouse model. To this end, we first investigated the presence of PN-like activity in C57BL/6J mice by recording AEPs during a fear-conditioning paradigm. Two alternating trains of tones, differing in stimulus duration, were presented on 7 subsequent days. One group received a mild foot shock delivered within the presentation of one train (conditioning train) on days 3-5 (conditioning days), while controls were never shocked. The fear-conditioned group (n= 9) indeed showed a PN-like activity during conditioning days manifested as a significant positive enhancement in the AEPs to the stimuli in the conditioning train that was not observed in the controls. The same paradigm was then applied to mice with reduced expression of the NMDAR1 (NR1) subunit and to a wild-type control group (each group n= 6). The NR1 mutants showed an associative AEP enhancement, but its magnitude was significantly reduced as compared with the magnitude in wild-type mice. We conclude that electrophysiological manifestations of selective attention are observable yet of different polarity in mice and that they require intact NMDAR-mediated signaling. Thus, deficient NMDAR functioning may contribute to abnormal selective attention in schizophrenia.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:August 2007
Deposited On:15 Mar 2009 18:57
Last Modified:02 May 2016 07:52
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1601-183X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1111/j.1601-183X.2006.00283.x
PubMed ID:17116169
Permanent URL: http://doi.org/10.5167/uzh-5907

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