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PMID:17582332

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Citation

Chubykin, AA, Atasoy, D, Etherton, MR, Brose, N, Kavalali, ET, Gibson, JR and Südhof, TC (2007) Activity-dependent validation of excitatory versus inhibitory synapses by neuroligin-1 versus neuroligin-2. Neuron 54:919-31

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.

Links

PubMed Online version:10.1016/j.neuron.2007.05.029

Keywords

Animals; Animals, Newborn; Benzylamines/pharmacology; Cell Adhesion Molecules, Neuronal; Cells, Cultured; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/drug effects; Excitatory Postsynaptic Potentials/physiology; Excitatory Postsynaptic Potentials/radiation effects; Gene Expression Regulation/physiology; Hippocampus/cytology; Inhibitory Postsynaptic Potentials/drug effects; Inhibitory Postsynaptic Potentials/physiology; Inhibitory Postsynaptic Potentials/radiation effects; Membrane Proteins/deficiency; Membrane Proteins/physiology; Nerve Tissue Proteins/deficiency; Nerve Tissue Proteins/physiology; Neural Inhibition/drug effects; Neural Inhibition/physiology; Neural Inhibition/radiation effects; Neurons/cytology; Neurons/physiology; Patch-Clamp Techniques; Protein Kinase Inhibitors/pharmacology; Rats; Receptors, AMPA/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Sulfonamides/pharmacology; Synapses/classification; Synapses/drug effects; Synapses/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:MTAP2

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NLGN1

located_in

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NLGN1

located_in

GO:0060076: excitatory synapse

ECO:0000305: curator inference used in manual assertion

GO:2000463

C

Seeded From UniProt

complete

RAT:NLGN1

located_in

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:NLGN2

located_in

GO:0060077: inhibitory synapse

ECO:0000305: curator inference used in manual assertion

GO:0097151

C

Seeded From UniProt

complete

MOUSE:NLGN1

located_in

GO:0060076: excitatory synapse

ECO:0000305: curator inference used in manual assertion

GO:2000463

C

Seeded From UniProt

complete

RAT:NLGN1

part_of

GO:0030425: dendrite

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NLGN1

part_of

GO:0045202: synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:NLGN1

NOT|involved_in

GO:0060080: inhibitory postsynaptic potential

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

part_of

GO:0060076: excitatory synapse

ECO:0000305: curator inference used in manual assertion

GO:2000463

C

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0051965: positive regulation of synapse assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:0060999: positive regulation of dendritic spine development

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:1902533: positive regulation of intracellular signal transduction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:2000310: regulation of NMDA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:2000311: regulation of AMPA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:NLGN1

involved_in

GO:2000463: positive regulation of excitatory postsynaptic potential

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:2000463: positive regulation of excitatory postsynaptic potential

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

involved_in

GO:2000310: regulation of NMDA receptor activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

NOT|involved_in

GO:0060080: inhibitory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:NLGN1

part_of

GO:0060076: excitatory synapse

ECO:0000305: curator inference used in manual assertion

GO:2000463

C

Seeded From UniProt

complete

MOUSE:NLGN2

part_of

GO:0060077: inhibitory synapse

ECO:0000305: curator inference used in manual assertion

GO:0097151

C

Seeded From UniProt

complete

MOUSE:NLGN2

involved_in

GO:0097151: positive regulation of inhibitory postsynaptic potential

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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