University of Massachusetts Medical School Faculty Publications

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Brudnick Neuropsychiatric Research Institute, Department of Neurobiology; Futai Lab; Graduate School of Biomedical Sciences, MD/PhD Program

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Amino Acids, Peptides, and Proteins | Neuroscience and Neurobiology


Synapse formation and regulation require signaling interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the alphaNrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic alphaNrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn signaling generates distinct functional properties at synapses.


electrophysiology, hippocampus, inhibitory interneuron, mouse, neuroscience, trans-synaptic adhesion

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Copyright © 2020, Uchigashima et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

DOI of Published Version



Uchigashima M, Konno K, Demchak E, Cheung A, Watanabe T, Keener DG, Abe M, Le T, Sakimura K, Sasaoka T, Uemura T, Imamura Kawasawa Y, Watanabe M, Futai K. Specific Neuroligin3-αNeurexin1 signaling regulates GABAergic synaptic function in mouse hippocampus. Elife. 2020 Dec 23;9:e59545. doi: 10.7554/eLife.59545. PMID: 33355091; PMCID: PMC7758064. Link to article on publisher's site

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Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.