RT Journal Article
SR Electronic
T1 Neuroligin3 Splice Isoforms Shape Mouse Hippocampal Inhibitory Synaptic Function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.22.915801
DO 10.1101/2020.01.22.915801
A1 Motokazu Uchigashima
A1 Ming Leung
A1 Takuya Watanabe
A1 Amy Cheung
A1 Masahiko Watanabe
A1 Yuka Imamura Kawasawa
A1 Kensuke Futai
YR 2020
UL http://biorxiv.org/content/early/2020/01/23/2020.01.22.915801.abstract
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.