PT  - JOURNAL ARTICLE
AU  - Motokazu Uchigashima
AU  - Ming Leung
AU  - Takuya Watanabe
AU  - Amy Cheung
AU  - Masahiko Watanabe
AU  - Yuka Imamura Kawasawa
AU  - Kensuke Futai
TI  - Neuroligin3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function
AID  - 10.1101/2020.01.22.915801
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.22.915801
4099  - http://biorxiv.org/content/early/2020/01/23/2020.01.22.915801.short
4100  - http://biorxiv.org/content/early/2020/01/23/2020.01.22.915801.full
AB  - 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.