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  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 26 ( 2008-07), p. 9087-9092
    Abstract: Neuroligin-1 is a potent trigger for the de novo formation of synaptic connections, and it has recently been suggested that it is required for the maturation of functionally competent excitatory synapses. Despite evidence for the role of neuroligin-1 in specifying excitatory synapses, the underlying molecular mechanisms and physiological consequences that neuroligin-1 may have at mature synapses of normal adult animals remain unknown. By silencing endogenous neuroligin-1 acutely in the amygdala of live behaving animals, we have found that neuroligin-1 is required for the storage of associative fear memory. Subsequent cellular physiological studies showed that suppression of neuroligin-1 reduces NMDA receptor-mediated currents and prevents the expression of long-term potentiation without affecting basal synaptic connectivity at the thalamo-amygdala pathway. These results indicate that persistent expression of neuroligin-1 is required for the maintenance of NMDAR-mediated synaptic transmission, which enables normal development of synaptic plasticity and long-term memory in the amygdala of adult animals.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 2 ( 2013-01-08), p. 725-730
    Abstract: Despite the pivotal functions of the NMDA receptor (NMDAR) for neural circuit development and synaptic plasticity, the molecular mechanisms underlying the dynamics of NMDAR trafficking are poorly understood. The cell adhesion molecule neuroligin-1 (NL1) modifies NMDAR-dependent synaptic transmission and synaptic plasticity, but it is unclear whether NL1 controls synaptic accumulation or function of the receptors. Here, we provide evidence that NL1 regulates the abundance of NMDARs at postsynaptic sites. This function relies on extracellular, NL1 isoform-specific sequences that facilitate biochemical interactions between NL1 and the NMDAR GluN1 subunit. Our work uncovers NL1 isoform-specific cis -interactions with ionotropic glutamate receptors as a key mechanism for controlling synaptic properties.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 32, No. 16 ( 2012-04-18), p. 5678-5687
    Abstract: MicroRNAs (miRNAs) have recently come to be viewed as critical players that modulate a number of cellular features in various biological systems including the mature CNS by exerting regulatory control over the stability and translation of mRNAs. Despite considerable evidence for the regulatory functions of miRNAs, the identities of the miRNA species that are involved in the regulation of synaptic transmission and plasticity and the mechanisms by which these miRNAs exert functional roles remain largely unknown. In the present study, the expression of microRNA-188 (miR-188) was found to be upregulated by the induction of long-term potentiation (LTP). The protein level of neuropilin-2 (Nrp-2), one of the possible molecular targets for miR-188, was decreased during LTP induction. We also confirmed that the luciferase activity of the 3′-UTR of Nrp-2 was diminished by treatment with a miR-188 oligonucleotide but not with a scrambled miRNA oligonucleotide. Nrp-2 serves as a receptor for semaphorin 3F, which is a negative regulator of spine development and synaptic structure. In addition, miR-188 specifically rescued the reduction in dendritic spine density induced by Nrp-2 expression in hippocampal neurons from rat primary culture. Furthermore, miR-188 counteracted the decrease in the miniature EPSC frequency induced by Nrp-2 expression in hippocampal neurons from rat primary culture. These findings suggest that miR-188 serves to fine-tune synaptic plasticity by regulating Nrp-2 expression.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2012
    detail.hit.zdb_id: 1475274-8
    SSG: 12
    Location Call Number Limitation Availability
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