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.
journal_name
Biol Psychiatryjournal_title
Biological psychiatryauthors
Tatard-Leitman VM,Jutzeler CR,Suh J,Saunders JA,Billingslea EN,Morita S,White R,Featherstone RE,Ray R,Ortinski PI,Banerjee A,Gandal MJ,Lin R,Alexandrescu A,Liang Y,Gur RE,Borgmann-Winter KE,Carlson GC,Hahn CG,Siegeldoi
10.1016/j.biopsych.2014.06.026subject
Has Abstractpub_date
2015-03-15 00:00:00pages
556-68issue
6eissn
0006-3223issn
1873-2402pii
S0006-3223(14)00518-6journal_volume
77pub_type
杂志文章abstract:BACKGROUND:Animal and human studies implicate forebrain neural circuits in maternal behavior. Here, we hypothesized that human brain response to emotional stimuli relevant for social interactions between infants and adults are modulated by sex- and experience-dependent factors. METHODS:We used functional magnetic reso...
journal_title:Biological psychiatry
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1983-02-01 00:00:00
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journal_title:Biological psychiatry
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journal_title:Biological psychiatry
pub_type: 杂志文章,评审
doi:10.1016/j.biopsych.2005.06.027
更新日期:2006-02-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
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journal_title:Biological psychiatry
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2017-01-15 00:00:00
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journal_title:Biological psychiatry
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更新日期:2013-08-15 00:00:00
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更新日期:2007-10-15 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:1998-02-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/s0006-3223(97)00355-7
更新日期:1998-05-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(87)90129-6
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journal_title:Biological psychiatry
pub_type: 杂志文章
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journal_title:Biological psychiatry
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更新日期:2000-09-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章
doi:10.1016/j.biopsych.2004.06.025
更新日期:2004-09-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/0006-3223(93)90195-j
更新日期:1993-10-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2010.03.017
更新日期:2010-07-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2009.12.032
更新日期:2010-06-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
doi:10.1016/j.biopsych.2015.04.024
更新日期:2015-12-15 00:00:00
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journal_title:Biological psychiatry
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0006-3223(00)01026-x
更新日期:2001-01-01 00:00:00
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journal_title:Biological psychiatry
pub_type: 杂志文章
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更新日期:2004-04-15 00:00:00