Behavioral characterization of dysbindin-1 deficient sandy mice

Bhardwaj, Sanjeev K.; Baharnoori, Moogeh; Sharif-Askari, Bahram; Kamath, Aarthi; Williams, Sylvain; Srivastava, Lalit K.

doi:10.1016/j.bbr.2008.10.011

Cited by 83 publications

(59 citation statements)

References 68 publications

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“…In particular, auditory-evoked high γ-activity correlated with both PPI and auditory S2/S1 ratio. Recent intracerebral recordings in humans have also associated hippocampal γ-activity with working memory capacity, and working memory is a behavior disrupted in the Dys1 −/− mouse (33,47,48,69). Thus, by extension, our findings suggest that γ-abnormalities may be associated with the working memory deficits found in the Dys1 −/− mouse.…”

Section: Role Of Disrupted Fast-phasic Inhibition In Reduced γ-Power supporting

confidence: 73%

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

Carlson

Talbot²,

Halene³

et al. 2011

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

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DTNBP1 (dystrobrevin binding protein 1) is a leading candidate susceptibility gene in schizophrenia and is associated with working memory capacity in normal subjects. In schizophrenia, the encoded protein dystrobrevin-binding protein 1 (dysbindin-1) is often reduced in excitatory cortical limbic synapses. We found that reduced dysbindin-1 in mice yielded deficits in auditory-evoked response adaptation, prepulse inhibition of startle, and evoked γ-activity, similar to patterns in schizophrenia. In contrast to the role of dysbindin-1 in glutamatergic transmission, γ-band abnormalities in schizophrenia are most often attributed to disrupted inhibition and reductions in parvalbumin-positive interneuron (PV cell) activity. To determine the mechanism underlying electrophysiological deficits related to reduced dysbindin-1 and the potential role of PV cells, we examined PV cell immunoreactivity and measured changes in net circuit activity using voltage-sensitive dye imaging. The dominant circuit impact of reduced dysbindin-1 was impaired inhibition, and PV cell immunoreactivity was reduced. Thus, this model provides a link between a validated candidate gene and an auditory endophenotypes. Furthermore, these data implicate reduced fast-phasic inhibition as a common underlying mechanism of schizophrenia-associated intermediate phenotypes.GABAergic | γ-oscillation | hippocampus | evoked response spectral perturbation | Sandy mouse P atients with schizophrenia have reduced amplitude and gating of auditory event-related potentials (ERPs) (1, 2). Recent clinical studies also show abnormal γ-band oscillations (30-100 Hz) as an endophenotype of the illness that is associated with reduced cognitive function (3-7). Work in animal models shows a prominent role of cortical inhibitory networks in generating γ-oscillations (8, 9), which in turn, supports the role of aberrant GABAergic inhibition as an important potential component of schizophrenia (4,7,10,11). The GABA-producing enzyme glutamic acid decarboxylase is dysregulated in schizophrenia, and postsynaptic GABA A receptors are dysregulated as well (4). Risk alleles for GABA A receptor subunits are also associated with the disease (12, 13), although linkage is weaker than the linkage found with dysbindin-1 and other candidate genes such as DISC1 (14). At the anatomical level, there is a loss of immunoreactivity for parvalbumin (PV) in schizophrenia. PV is a calcium-binding protein marker for a class of fast-spiking GABAergic neurons. It is debated whether reduced PV in postmortem studies is caused by reduction in cell number or merely loss of protein expression. In either case, reduced PV immunoreactivity suggests disruption of an important source of local circuit inhibition (4, 15).Although clinical electrophysiological and postmortem anatomical findings support the role of GABA dysfunction in schizophrenia, a larger set of schizophrenia risk haplotypes are thought to confer reduced NMDA receptor-mediated function and changes in glutamatergic transmission [e.g., DISC1; Neuregu...

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Section: Role Of Disrupted Fast-phasic Inhibition In Reduced γ-Power supporting

confidence: 73%

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

Carlson

Talbot²,

Halene³

et al. 2011

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

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“…In humans, DTNBP1 SNPs and haplotypes have been associated with the cognitive deficits or negative symptoms (45), although its relationship with dysbindin-1 isoforms is unknown. Similarly, in sdy mice, social withdrawal, recognition deficits, altered memory capacities, or contextual fear conditioning have been reported, which may be related to dysfunction in adult hippocampal neurogenesis (11,14,31). Our additional tests on pattern separation in this study further suggest that impaired adult hippocampal neurogenesis plays an important role in the development of these cognitive deficits.…”

Section: Discussionmentioning

confidence: 99%

“…It has shown that the sandy (sdy) mouse, which arose on the DBA/2J inbred strain and carries a spontaneously occurring large deletion (ϳ38 kb), which spans intron 5 to intron 7 in the Dtnbp1 gene (10), is a mouse model of schizophrenia (11)(12)(13)(14). Neuronal differentiation of adult-born neurons in the dentate gyrus (DG) 2 is impaired in sdy mice, although the underlying mechanism is unclear (15).…”

mentioning

confidence: 99%

Dysbindin-1C Is Required for the Survival of Hilar Mossy Cells and the Maturation of Adult Newborn Neurons in Dentate Gyrus

Wang

Yuan

Zhang

et al. 2014

Journal of Biological Chemistry

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Background: Dysbindin-1 isoforms are selectively reduced in schizophrenic brains. Results: Dysbindin-1C is required for the survival of hilar mossy cells and the maturation of adult newborn neurons in the dentate gyrus. Conclusion: Dysbindin-1C, but not -1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner. Significance: Reduced dysbindin-1C in the schizophrenic hippocampal formation likely contributes to the development of cognitive deficits.

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“…DTNBP1 (dystrobrevin-binding protein 1), which encodes dysbindin-1, is a leading susceptibility gene of SCZ (Straub et al, 2002;Fanous and Kendler, 2008). The sandy (sdy) mutant, which carries a spontaneously occurring large deletion in the Dtnbp1 gene on the DBA/2J inbred strain (Li et al, 2003), is an appropriate mouse model of SCZ Hattori et al, 2008;Takao et al, 2008;Bhardwaj et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Impaired Autophagy in Hilar Mossy Cells of the Dentate Gyrus and Its Implication in Schizophrenia

Yuan

Wang

Wei

et al. 2015

Journal of Genetics and Genomics

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Behavioral characterization of dysbindin-1 deficient sandy mice

Cited by 83 publications

References 68 publications

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia

Dysbindin-1C Is Required for the Survival of Hilar Mossy Cells and the Maturation of Adult Newborn Neurons in Dentate Gyrus

Impaired Autophagy in Hilar Mossy Cells of the Dentate Gyrus and Its Implication in Schizophrenia

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