UMMS Affiliation

Department of Neurobiology; Graduate School of Biomedical Sciences; Futai Lab

Publication Date

2020-05-07

Document Type

Article Postprint

Disciplines

Amino Acids, Peptides, and Proteins | Cell Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience | Molecular Biology | Nervous System | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, transsynaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate Neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

Keywords

CA1 pyramidal neuron, GABA receptor, excitatory and inhibitory balance, glutamate receptor, hippocampus, neurobiology, neuroligin 3 (NLGN3), neuron, neurotransmitter receptor, splice variants, synapse, trans-synaptic cell adhesion

Rights and Permissions

Accepted manuscript ("paper in press") plus supporting information posted as allowed by publisher's copyright policy at https://www.asbmb.org/journals-news/editorial-policies.

DOI of Published Version

10.1074/jbc.AC120.012571

Source

Uchigashima M, Leung M, Watanabe T, Cheung A, Le T, Pallat S, Dinis ALM, Watanabe M, Imamura Kawasawa Y, Futai K. Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus. J Biol Chem. 2020 May 7:jbc.AC120.012571. doi: 10.1074/jbc.AC120.012571. Epub ahead of print. PMID: 32381505. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of biological chemistry

Related Resources

Link to Article in PubMed

PubMed ID

32381505

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