Journal article
Activity-Dependent Validation of Excitatory versus Inhibitory Synapses by Neuroligin-1 versus Neuroligin-2
Neuron (Cambridge, Mass.), Vol.54(6), pp.919-931
2007
DOI: 10.1016/j.neuron.2007.05.029
PMID: 17582332
Abstract
Neuroligins enhance synapse formation in vitro, but surprisingly are not required for the generation of synapses in vivo. We now show that in cultured neurons, neuroligin-1 overexpression increases excitatory, but not inhibitory, synaptic responses, and potentiates synaptic NMDAR/AMPAR ratios. In contrast, neuroligin-2 overexpression increases inhibitory, but not excitatory, synaptic responses. Accordingly, deletion of neuroligin-1 in knockout mice selectively decreases the NMDAR/AMPAR ratio, whereas deletion of neuroligin-2 selectively decreases inhibitory synaptic responses. Strikingly, chronic inhibition of NMDARs or CaM-Kinase II, which signals downstream of NMDARs, suppresses the synapse-boosting activity of neuroligin-1, whereas chronic inhibition of general synaptic activity suppresses the synapse-boosting activity of neuroligin-2. Taken together, these data indicate that neuroligins do not establish, but specify and validate, synapses via an activity-dependent mechanism, with different neuroligins acting on distinct types of synapses. This hypothesis reconciles the overexpression and knockout phenotypes and suggests that neuroligins contribute to the use-dependent formation of neural circuits.
Details
- Title: Subtitle
- Activity-Dependent Validation of Excitatory versus Inhibitory Synapses by Neuroligin-1 versus Neuroligin-2
- Creators
- Alexander A Chubykin - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USADeniz Atasoy - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USAMark R Etherton - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USANils Brose - Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USAEge T Kavalali - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USAJay R Gibson - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USAThomas C Südhof - Department of Neuroscience, The University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.54(6), pp.919-931
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.neuron.2007.05.029
- PMID
- 17582332
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Grant note
- DOI: 10.13039/100000025, name: National Institute of Mental Health, award: R37 MH52804-08
- Language
- English
- Date published
- 2007
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984040339602771
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