Cell Type-Specific Development of NMDA Receptors in the Interneurons of Rat Prefrontal Cortex

Wang, Huai-Xing; Gao, Wen-Jun

doi:10.1038/npp.2009.20

Cited by 191 publications

(238 citation statements)

References 108 publications

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“…In adult rats, the majority of fast-spiking interneurons are devoid of NMDA receptors, whereas NMDAR dependent synaptic excitation is more significant in other subclasses of regularspiking and low-threshold spiking inhibitory cells (Wang and Gao 2009). The latter mediate dendritic inhibition, thereby gating synaptic inputs onto pyramidal cells.…”

Section: Biophysically-based Neural Circuit Modeling: Understanding Amentioning

confidence: 99%

Computational Psychiatry

2016

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Psychiatric disorders such as autism and schizophrenia arise from abnormalities in brain systems that underlie cognitive, emotional and social functions. The brain is enormously complex and its abundant feedback loops on multiple scales preclude intuitive explication of circuit functions. In close interplay with experiments, theory and computational modeling are essential for understanding how, precisely, neural circuits generate flexible behaviors and their impairments give rise to psychiatric symptoms. This Perspective highlights recent progress in applying computational neuroscience to the study of mental disorders. We outline basic approaches, including identification of core deficits that cut across disease categories, biologically-realistic modeling bridging cellular and synaptic mechanisms with behavior, model-aided diagnosis. The need for new research strategies in psychiatry is urgent. Computational psychiatry potentially provides powerful tools for elucidating pathophysiology that may inform both diagnosis and treatment. To achieve this promise will require investment in cross-disciplinary training and research in this nascent field. © 2014 Elsevier Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Neither Dr. Wang nor Dr. Krystal has any financial interests relevant to the advancement of computational psychiatry. to and engage with psychiatric research. Second, it will be important to develop a cadre of young psychiatrists who learn computational modeling, lest computational psychiatry.

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Section: Biophysically-based Neural Circuit Modeling: Understanding Amentioning

confidence: 99%

Computational Psychiatry

2016

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“…One concerns the relationship between the late maturation of E/I-balance parameters, neural synchrony and the manifestation of the disorder (Figure 2). Evidence has accumulated that points towards important modifications in neurotransmitter-systems supporting high-frequency oscillations during adolescence [51][52][53]. Furthermore, developmental data on neural synchrony has highlighted that cortical circuits during late brain maturation are accompanied by profound modifications in the amplitude and synchrony at theta-, beta-, and gamma-frequencies [54].…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

Uhlhaas

2013

Current Opinion in Neurobiology

157

143

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“…There are three types of interneurons in PFC: fast-spiking (FS), regular spiking (RS), and low-threshold spiking (LTS) (18)(19)(20)(21). RS and LTS interneurons are also called Non-FS interneurons.…”

Section: In Contrast In Dysmentioning

confidence: 99%

Role of dysbindin in dopamine receptor trafficking and cortical GABA function

Ji¹,

Yang²,

Papaleo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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131

154

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Dysbindin has been implicated in the pathogenesis of schizophrenia, but little is known about how dysbindin affects neuronal function in the circuitry underlying psychosis and related behaviors. Using a dysbindin knockout line (dys ؊/؊ ) derived from the natural dysbindin mutant Sandy mice, we have explored the role of dysbindin in dopamine signaling and neuronal function in the prefrontal cortex (PFC). Combined cell imaging and biochemical experiments revealed a robust increase in the dopamine receptor D2, but not D1, on cell surface of neurons from dys ؊/؊ cortex. This was due to an enhanced recycling and insertion, rather than reduced endocytosis, of D2. Disruption of dysbindin gene resulted in a marked decrease in the excitability of fast-spiking (FS) GABAergic interneurons in both PFC and striatum. Dys ؊/؊ mice also exhibited a decreased inhibitory input to pyramidal neurons in layer V of PFC. The increased D2 signaling in dys ؊/؊ FS interneurons was associated with a more pronounced increase in neuronal firing in response to D2 agonist, compared to that in wild-type interneurons. Taken together, these results suggest that dysbindin regulates PFC function by facilitating D2-mediated modulation of GABAergic function.dopamine D2 receptor ͉ schizophrenia ͉ prefrontal cortex G enetic variants in a gene on 6p22.3, dysbindin (DTNBP1), have been shown to be one of the several genes that are associated with schizophrenia (1). Schizophrenia patients have significantly reduced expression of dysbindin mRNA and protein in prefrontal cortex and hippocampus (2, 3). While it remains unclear how changes in dysbindin expression could contribute to the pathogenesis of schizophrenia, cell biological studies have begun to address the physiological function of dysbindin in neurons. Downregulation of dysbindin by siRNA in cultured neurons leads to decreases in the expression of SNAP25 and levels of extracellular glutamate or dopamine (4, 5). Dysbindin contributes to normal biogenesis of lysosome-related organelles (LROs) by binding to proteins in the BLOC-1 complex (6, 7), which regulates trafficking of LROs. The Sandy mouse (Sdy), which harbors an in-frame deletion of two exons of the dysbindin gene (8), exhibits a reduced readily releasable pool of synaptic vesicles and larger vesicle size (9). Although dysbindin protein is localized both pre-and postsynaptically (7), little is known about its postsynaptic function. Recently, downregulation of dysbindin has been shown to increase cell surface expression of dopamine receptor D2 (D2), but not dopamine receptor D1 (D1), in human SH-SY5Y neuroblastoma cells and in cultured cortical neurons (10). Dopamine receptor internalization (or endocytosis) is a general mechanism to adjust neuronal responses to dopamine stimulation. Both D1 and D2 are G protein coupled receptors (GPCRs) that undergo constitutive and ligand-induced internalization. Unlike D1, which is recycled back to the plasma membrane after endocytosis, D2 is generally trafficked to the lysosomal pathway and degraded (11)(1...

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Cell Type-Specific Development of NMDA Receptors in the Interneurons of Rat Prefrontal Cortex

Cited by 191 publications

References 108 publications

Computational Psychiatry

Computational Psychiatry

Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia

Role of dysbindin in dopamine receptor trafficking and cortical GABA function

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