TableEdit

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

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.

PubMed Online version:10.1016/j.neuron.2007.05.029

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