Neuroligin-3 Regulates Excitatory Synaptic Transmission and EPSP-Spike Coupling in the Dentate Gyrus In Vivo

Mol Neurobiol. 2022 Feb;59(2):1098-1111. doi: 10.1007/s12035-021-02663-9. Epub 2021 Nov 29.


Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.

Keywords: Autism Spectrum disorder; In vivo electrophysiology; Neuroligins; Synaptic transmission; Synaptosomal preparation.

MeSH terms

  • Animals
  • Autism Spectrum Disorder
  • Cell Adhesion Molecules, Neuronal* / genetics
  • Dentate Gyrus* / physiology
  • Excitatory Postsynaptic Potentials*
  • Membrane Proteins* / genetics
  • Mice
  • Nerve Tissue Proteins* / genetics
  • Synaptic Transmission*


  • Cell Adhesion Molecules, Neuronal
  • Membrane Proteins
  • Nerve Tissue Proteins
  • neuroligin 3