AI Article Synopsis
- * Neurons without FBXO41 maintain normal structure but show impaired synaptic transmission, with excitatory neurons releasing fewer synaptic vesicles and inhibitory neurons having decreased functional properties.
- * During brain development, FBXO41 loss results in reduced size and cellularity in specific brain regions and delays in neuronal migration and activity, indicating its importance in early brain function.
Article Abstract
FBXO41 is a neuron-specific E3 ligase subunit implicated in epileptic encephalopathies. null mutant (KO) mice show behavioral deficits and early lethality. Here, we report that loss of FBXO41 causes defects in synaptic transmission and brain development. Cultured KO 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. In KO 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 in KO mice.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971942 | PMC |
| http://dx.doi.org/10.1016/j.isci.2022.104069 | DOI Listing |
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