The schizophrenia susceptibility gene DTNBP1 modulates AMPAR synaptic transmission and plasticity in the hippocampus of juvenile DBA/2J mice

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• 作者：Ian J. Orozco ; Peter Koppensteiner ; Ipe Ninan ; Ottavio Arancio
• 关键词：AMPAR ; 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid receptor ; NMDAR ; N-Methyl-d-aspartic acid receptor ; LTP ; Long-term potentiation
• 刊名：Molecular and Cellular Neuroscience
• 出版年：January, 2014
• 年：2014
• 卷：58
• 期：Complete
• 页码：76-84
• 全文大小：1054 K

文摘

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.