title: Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.
abstract: Neuroligins (Nlgns) are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT) littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8-12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.
authors.affiliation: Department of Physiology and Biophysics and Rappaport Institute, Technion Faculty of Medicine, and Network Biology Research Laboratories, Lorry Lokey Center for Life Sciences and Engineering, Haifa, Israel.
authors.forename: Adel
authors.initials: A
authors.lastname: Zeidan
authors.forename: Noam E
authors.initials: NE
authors.lastname: Ziv
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D005456:Fluorescent Dyes; D051528:Guanylate Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013569:Synapses / Q000502:physiology*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005456:Fluorescent Dyes; D008565:Membrane Proteins; C093438:neuroligin 1; D051528:Guanylate Kinases