Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes
Juan E. Belforte,Veronika Zsiros,Elyse R Sklar,Zhihong Jiang,Gu Yu,Yuqing Li,Elizabeth M. Quinlan,Kazu Nakazawa +7 more
TLDR
It is suggested that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.Abstract:
Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40-50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.read more
Citations
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Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis
Josep Dalmau,Eric Lancaster,Eugenia Martinez-Hernandez,Myrna R. Rosenfeld,Rita J. Balice-Gordon +4 more
TL;DR: Patients' antibodies cause a titre-dependent, reversible decrease of synaptic NMDAR by a mechanism of crosslinking and internalisation, which reveals a probable pathogenic relation between the depletion of receptors and the clinical features of anti-NMDAR encephalitis.
Journal ArticleDOI
NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease
TL;DR: The effects of subunit composition on NMDAR properties, synaptic plasticity and cellular mechanisms implicated in neuropsychiatric disorders are reviewed and could provide new therapeutic strategies against dysfunctions of glutamatergic transmission.
Journal ArticleDOI
Neocortical excitation/inhibition balance in information processing and social dysfunction
Ofer Yizhar,Ofer Yizhar,Lief E. Fenno,Matthias Prigge,Franziska Schneider,Thomas J. Davidson,Daniel J. O’Shea,Vikaas S. Sohal,Vikaas S. Sohal,Inbal Goshen,Joel Finkelstein,Jeanne T. Paz,Katja Stehfest,Roman Fudim,Charu Ramakrishnan,John R. Huguenard,Peter Hegemann,Karl Deisseroth +17 more
TL;DR: In this article, the authors design and use several optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology.
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Neurophysiological and Computational Principles of Cortical Rhythms in Cognition
TL;DR: A plethora of studies will be reviewed on the involvement of long-distance neuronal coherence in cognitive functions such as multisensory integration, working memory, and selective attention, and implications of abnormal neural synchronization are discussed as they relate to mental disorders like schizophrenia and autism.
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Animal models of neuropsychiatric disorders
Eric J. Nestler,Steven E. Hyman +1 more
TL;DR: The current state of animal models of mental illness, with a focus on schizophrenia, depression and bipolar disorder, is reviewed and it is argued for areas of focus that might increase the likelihood of creating more useful models, at least for some disorders.
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