Neuroligin-1 regulates excitatory synaptic transmission, LTP and EPSP-spike coupling in the dentate gyrus in vivo
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  • 作者:Peter Jedlicka (1)
    Matej Vnencak (1)
    Dilja D. Krueger (2)
    Tassilo Jungenitz (1)
    Nils Brose (2)
    Stephan W. Schwarzacher (1)

    1. Institute of Clinical Neuroanatomy
    ; Neuroscience Center ; Goethe-University Frankfurt ; Theodor-Stern Kai 7 ; 60590 ; Frankfurt ; Germany
    2. Department of Molecular Neurobiology
    ; Max Planck Institute of Experimental Medicine ; 37075 ; G枚ttingen ; Germany
  • 关键词:Dentate granule cells ; Perforant path ; Excitability ; Synaptic plasticity ; Paired ; pulse inhibition ; Cell adhesion molecule
  • 刊名:Brain Structure and Function
  • 出版年:2015
  • 出版时间:January 2015
  • 年:2015
  • 卷:220
  • 期:1
  • 页码:47-58
  • 全文大小:2,450 KB
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  • 刊物主题:Neurosciences; Cell Biology; Neurology;
  • 出版者:Springer Berlin Heidelberg
  • ISSN:1863-2661
文摘
Neuroligins are transmembrane cell adhesion proteins with a key role in the regulation of excitatory and inhibitory synapses. Based on previous in vitro and ex vivo studies, neuroligin-1 (NL1) has been suggested to play a selective role in the function of glutamatergic synapses. However, the role of NL1 has not yet been investigated in the brain of live animals. We studied the effects of NL1-deficiency on synaptic transmission in the hippocampal dentate gyrus using field potential recordings evoked by perforant path stimulation in urethane-anesthetized NL1 knockout (KO) mice. We report that in NL1 KOs the activation of glutamatergic perforant path granule cell inputs resulted in reduced synaptic responses. In addition, NL1 KOs displayed impairment in long-term potentiation. Furthermore, field EPSP-population spike (E-S) coupling was greater in NL1 KO than WT mice and paired-pulse inhibition was reduced, indicating a compensatory rise of excitability in NL1 KO granule cells. Consistent with changes in excitatory transmission, NL1 KOs showed a significant reduction in hippocampal synaptosomal expression levels of the AMPA receptor subunit GluA2 and NMDA receptor subunits GluN1, GluN2A and GluN2B. Taken together, we provide first evidence that NL1 is essential for normal excitatory transmission and long-term synaptic plasticity in the hippocampus of intact animals. Our data provide insights into synaptic and circuit mechanisms of neuropsychiatric abnormalities such as learning deficits and autism.

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