RGD Reference Report - Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. - Rat Genome Database

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Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2.

Authors: Chubykin, AA  Atasoy, D  Etherton, MR  Brose, N  Kavalali, ET  Gibson, JR  Sudhof, TC 
Citation: Chubykin AA, etal., Neuron. 2007 Jun 21;54(6):919-31.
RGD ID: 8553502
Pubmed: PMID:17582332   (View Abstract at PubMed)
PMCID: PMC3738748   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2007.05.029   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process


Cellular Component

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Map2Ratdendrite located_inIDA PMID:17582332BHF-UCL 
Nlgn1Ratdendrite located_inIDA PMID:17582332BHF-UCL 
Nlgn1Ratexcitatory synapse located_inICGO:2000463PMID:17582332BHF-UCL 
Nlgn1Ratexcitatory synapse part_ofNAS PMID:17582332ComplexPortal 
Nrxn1Ratexcitatory synapse part_ofNAS PMID:17582332ComplexPortal 
Nlgn1Ratinhibitory synapse part_ofNAS PMID:17582332ComplexPortal 
Nrxn1Ratinhibitory synapse part_ofNAS PMID:17582332ComplexPortal 
Nlgn1Ratsynapse located_inIDA PMID:17582332BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Map2  (microtubule-associated protein 2)
Nlgn1  (neuroligin 1)
Nrxn1  (neurexin 1)

Additional Information