Attenuated bidirectional short-term synaptic plasticity in the dentate gyrus of Schnurri-2 knockout mice, a model of schizophrenia 11 Medical and Health Sciences 1109 Neurosciences 11 Medical and Health Sciences 1103 Clinical Sciences

Katsunori Kobayashi, Tsuyoshi Takagi, Shunsuke Ishii, Hidenori Suzuki, Tsuyoshi Miyakawa

Research output: Contribution to journalArticle

Abstract

The dentate gyrus of the hippocampus has been implicated in the pathophysiological basis of neuropsychiatric disorders including schizophrenia. We have identified several mouse models of neuropsychiatric disorders with robust molecular and functional defects in the dentate gyrus. Among them, mice lacking Schnurri-2 (Shn2 or HIVEP2) have been proposed as a model of schizophrenia and intellectual disability. Shn2 knockout mice exhibit behavioral abnormalities resembling symptoms of schizophrenia and HIVEP2-related intellectual disability as well as marked functional alterations in the soma and output synapse of the dentate granule cells (GCs). Although robust abnormalities were also observed in the dendritic spine morphology in the GCs, their functional correlates remain unknown. In the present study, we performed electrophysiological analyses of synaptic transmission at the medial perforant path (MPP) input onto the GCs in Shn2 knockout mice. While the basal synaptic efficacy was preserved, short-term synaptic depression induced by paired-pulse or low-frequency stimulation was reduced in the mutant mice. High-frequency tetanic stimulation induced lasting synaptic potentiation in both wild-type and mutant mice. However, the decaying synaptic potentiation shortly after the tetanic stimulation was significantly reduced in the mutant mice. These results indicate that the Shn2 deficiency attenuates bidirectional short-term synaptic plasticity at the MPP-GC synapse, thereby rendering the synapse more static. Our finding further supports a possible role of the dentate gyrus dysfunction in pathophysiology of schizophrenia and may also provide important information in interpreting morphology changes of the brain synapses in neuropsychiatric disorders.

Original languageEnglish
Article number56
JournalMolecular Brain
Volume11
Issue number1
DOIs
Publication statusPublished - 01-10-2018

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Neuronal Plasticity
Dentate Gyrus
Neurosciences
Knockout Mice
Schizophrenia
Synapses
Health
Perforant Pathway
Intellectual Disability
Parahippocampal Gyrus
Dendritic Spines
Carisoprodol
Synaptic Transmission
Brain

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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abstract = "The dentate gyrus of the hippocampus has been implicated in the pathophysiological basis of neuropsychiatric disorders including schizophrenia. We have identified several mouse models of neuropsychiatric disorders with robust molecular and functional defects in the dentate gyrus. Among them, mice lacking Schnurri-2 (Shn2 or HIVEP2) have been proposed as a model of schizophrenia and intellectual disability. Shn2 knockout mice exhibit behavioral abnormalities resembling symptoms of schizophrenia and HIVEP2-related intellectual disability as well as marked functional alterations in the soma and output synapse of the dentate granule cells (GCs). Although robust abnormalities were also observed in the dendritic spine morphology in the GCs, their functional correlates remain unknown. In the present study, we performed electrophysiological analyses of synaptic transmission at the medial perforant path (MPP) input onto the GCs in Shn2 knockout mice. While the basal synaptic efficacy was preserved, short-term synaptic depression induced by paired-pulse or low-frequency stimulation was reduced in the mutant mice. High-frequency tetanic stimulation induced lasting synaptic potentiation in both wild-type and mutant mice. However, the decaying synaptic potentiation shortly after the tetanic stimulation was significantly reduced in the mutant mice. These results indicate that the Shn2 deficiency attenuates bidirectional short-term synaptic plasticity at the MPP-GC synapse, thereby rendering the synapse more static. Our finding further supports a possible role of the dentate gyrus dysfunction in pathophysiology of schizophrenia and may also provide important information in interpreting morphology changes of the brain synapses in neuropsychiatric disorders.",
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