RT Journal Article
SR Electronic
T1 Increased Network Inhibition in the Dentate Gyrus of Adult Neuroligin-4 Knock-Out Mice
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0471-22.2023
DO 10.1523/ENEURO.0471-22.2023
VO 10
IS 4
A1 Julia Muellerleile
A1 Matej Vnencak
A1 Mohammad Valeed Ahmed Sethi
A1 Tassilo Jungenitz
A1 Stephan W. Schwarzacher
A1 Peter Jedlicka
YR 2023
UL http://www.eneuro.org/content/10/4/ENEURO.0471-22.2023.abstract
AB Loss-of-function mutations in neuroligin-4 (Nlgn4), a member of the neuroligin family of postsynaptic adhesion proteins, cause autism spectrum disorder in humans. Nlgn4 knockout (KO) in mice leads to social behavior deficits and complex alterations of synaptic inhibition or excitation, depending on the brain region. In the present work, we comprehensively analyzed synaptic function and plasticity at the cellular and network levels in hippocampal dentate gyrus of Nlgn4 KO mice. Compared with wild-type littermates, adult Nlgn4 KO mice exhibited increased paired-pulse inhibition of dentate granule cell population spikes, but no impairments in excitatory synaptic transmission or short-term and long-term plasticity in vivo. In vitro patch-clamp recordings in neonatal organotypic entorhino-hippocampal slice cultures from Nlgn4 KO and wild-type littermates revealed no significant differences in excitatory or inhibitory synaptic transmission, homeostatic synaptic plasticity, and passive electrotonic properties in dentate granule cells, suggesting that the increased inhibition in vivo is the result of altered network activity in the adult Nlgn4 KO. A comparison with prior studies on Nlgn 1–3 knock-out mice reveals that each of the four neuroligins exerts a characteristic effect on both intrinsic cellular and network activity in the dentate gyrus in vivo.