摘要：SummaryFBXO41 is a neuron-specific E3 ligase subunit implicated in epileptic encephalopathies.Fbxo41null mutant (KO) mice show behavioral deficits and early lethality. Here, we report that loss of FBXO41 causes defects in synaptic transmission and brain development. CulturedFbxo41KO neurons had normal morphology and showed no signs of degeneration. Single-cell electrophysiology showed a lower synaptic vesicle release probability in excitatory neurons. Inhibitory neurons exhibited reduced synaptophysin expression, a smaller readily releasable pool, and decreased charge transfer during repetitive stimulation. InFbxo41KO hippocampal slices at postnatal day 6, the dentate gyrus was smaller with fewer radial-glial-like cells and immature neurons. In addition, neuronal migration was delayed. Two-photon calcium imaging showed a delayed increase in network activity and synchronicity. Together, our findings point toward a role for FBXO41 in synaptic transmission and postnatal brain development, before behavioral deficits are detected inFbxo41KO mice.Graphical abstractDisplay OmittedHighlights•FBXO41 controls synaptic transmission in excitatory and inhibitory neurons differently•Fbxo41KO hippocampi are smaller, with fewer radial-glial-like cells and immature neurons•Fbxo41KO hippocampus shows neuronal migration and network maturation defects•FBXO41 plays a critical role in neuronal transmission and postnatal brain developmentMolecular neuroscience; Developmental neuroscience; Cellular neuroscience
