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Hippocampus v.27 no.3, 2017년, pp.235 - 248   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

The sorting receptor SorCS3 is a stronger regulator of glutamate receptor functions compared to GABAergic mechanisms in the hippocampus

Christiansen, Gitte B. (Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Andersen, Katrine H. (Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Riis, Sarah (Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Nykjaer, Anders (DANDRITE, Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Bolcho, Ulrik (DANDRITE, Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Jensen, Morten S. (Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ; Holm, Mai Marie (Department of Biomedicine, Aarhus University, Aarhus, Denmark ) ;
  • 초록  

    ABSTRACT Correct function of glutamate receptors in the postsynaptic density is crucial to synaptic function and plasticity. SorCS3 (sortilin‐related receptor CNS expressed 3) is a sorting receptor which previously has been shown to interact with the key postsynaptic proteins; PSD‐95 and PICK1. In this study, we employed electrophysiological analyses of acute brain slices combined with immunohistochemistry to define the role of SorCS3 in hippocampal synapses in CA1 and the dentate gyrus. We analyzed a juvenile (P17‐21) and a young adult (P55‐65) group of animals from a Sorcs3 knockout mouse model. We show that the basal synaptic transmission is severely affected in SorCS3‐deficient neurons in CA1, while only slightly reduced in the dentate gyrus. Specifically, input/output curves of CA1 synapses revealed a 20% reduction of fEPSP (field excitatory postsynaptic potential) slopes at the highest stimulation intensity in knockouts of the juvenile group, which developed to a 33% decrease in young adult animals. These impairments may be a result of changes in the postsynaptic AMPA receptors. Interestingly, repetitive afferent stimulation demonstrated that SorCS3‐deficient slices respond with an enhanced synaptic facilitation and reduced synaptic depression. These changes also developed with age. A molecular mechanism underlying this relative increase during repetitive stimulations is compatible with enhanced mobility of postsynaptic AMPA receptors resulting in faster exchange of desensitized receptors in the postsynaptic density. The altered response during repetitive stimulation was characteristic for CA1 but not the dentate gyrus. Immunohistochemical analyses of parvalbumin positive neurons combined with paired‐pulse tests of network inhibition and patch‐clamp recordings only showed minute inhibitory changes in SorCS3‐deficient slices. Our results suggest that SorCS3 serves an important role in the postsynaptic protein network, which is more pronounced in CA1 compared to the dentate gyrus. These data support a role for SorCS3 in controlling proper positioning and mobility of glutamate receptors in the postsynaptic density. ⓒ 2016 Wiley Periodicals, Inc.


  • 주제어

    hippocampus .   sortilin .   synaptic transmission .   glutamate receptor .   synaptic plasticity.  

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