title: The schizophrenia susceptibility gene DTNBP1 modulates AMPAR synaptic transmission and plasticity in the hippocampus of juvenile DBA/2J mice.
abstract: The dystrobrevin binding protein (DTNBP) 1 gene has emerged over the last decade as a potential susceptibility locus for schizophrenia. While no causative mutations have been found, reduced expression of the encoded protein, dysbindin, was reported in patients. Dysbindin likely plays a role in the neuronal trafficking of proteins including receptors. One important pathway suspected to be affected in schizophrenia is the fast excitatory glutamatergic transmission mediated by AMPA receptors. Here, we investigated excitatory synaptic transmission and plasticity in hippocampal neurons from dysbindin-deficient sandy mice bred on the DBA/2J strain. In cultured neurons an enhancement of AMPAR responses was observed. The enhancement of AMPAR-mediated transmission was confirmed in hippocampal CA3-CA1 synapses, and was not associated with changes in the expression of GluA1-4 subunits or an increase in GluR2-lacking receptor complexes. Lastly, an enhancement in LTP was also found in these mice. These data provide compelling evidence that dysbindin, a widely suspected susceptibility protein in schizophrenia, is important for AMPAR-mediated synaptic transmission and plasticity in the developing hippocampus.
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. Electronic address: ian.orozco@mdc-berlin.de.
authors: Ian J
authors: IJ
authors: Orozco
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.
authors: Peter
authors: P
authors: Koppensteiner
authors: Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors: Ipe
authors: I
authors: Ninan
authors: Department of Pathology and Cell Biology, Columbia University, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. Electronic address: oa1@columbia.edu.
authors: Ottavio
authors: O
authors: Arancio
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D017774:Long-Term Potentiation; D051379:Mice; D008811:Mice, Inbred DBA; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics; D009435:Synaptic Transmission
chemical_list: D002352:Carrier Proteins; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D018091:Receptors, AMPA; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AMPAR; DTNBP1; Dysbindin; LTP; Schizophrenia