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bioRxiv · 10.1101/2020.01.22.915801

Neuroligin3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function

Uchigashima, M.·Leung, M.·Watanabe, T.·Cheung, A.·Watanabe, M.·Imamura Kawasawa, Y.·Futai, K.
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Abstract

Synapse formation is a dynamic process essential for neuronal circuit development and maturation. At the synaptic cleft, trans-synaptic protein-protein interactions constitute major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity. Dysregulation of the E-I balance has been implicated in neurodevelopmental disorders including autism spectrum disorders. However, the molecular mechanisms underlying E-I balance remain to be elucidated. Here, we investigate Neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that Nlgn3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. Distinct subcellular localization patterns of Nlgn3 isoforms contribute to the functional differences observed among splice variants. Finally, single-cell sequencing analysis reveals that Nlgn1 and Nlgn3 are the major Nlgn genes and that expression of Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons.

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Uchigashima, M., Leung, M., Watanabe, T., Cheung, A., Watanabe, M., Imamura Kawasawa, Y., Futai, K.. 2020-01-23. Neuroligin3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function. https://doi.org/10.1101/2020.01.22.915801

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