Abstract
Members of the neuroligin family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, the function of neuroligins in vivo in the regulation of synapse formation and synapse number has been difficult to establish. We found that neuroligin-1 (NL1), which is located at excitatory postsynaptic densities, regulates activity-dependent synaptogenesis and mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number was not sensitive to absolute NL1 levels but instead depended on transcellular differences in the relative amounts of NL1. These effects were independent of the cell-autonomous regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data indicate that transcellular competitive processes govern synapse formation and number in developing cortex and that NL1 has a central function in these processes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1667-1674 |
| Number of pages | 8 |
| Journal | Nature neuroscience |
| Volume | 15 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2012 |
Funding
We thank members of the Sabatini laboratory for their constructive comments on the manuscript. We also thank A. Giessel, J.F. Sturgill and B. Bloodgood for helping us with data analysis. We are grateful to F. Varoqueaux and N. Brose (Max Planck Institute for Experimental Medicine) for providing mouse NL1 expression vector and Nlgn1+/− mice. This work was supported by US National Institutes of Health grant R01NS064583 (to C.G.), a Leonard and Isabelle Goldenson Research Fellowship (to Y.K.) and a SFARI grant from the Simons Foundation (to B.L.S.).
ASJC Scopus subject areas
- General Neuroscience