Core PCP protein Vangl2 is essential to the structural and functional development of the hippocampal mossy fiber bouton/thorny excrescences (MfB/TE) synapse.
Résumé
Our team previously showed that the four transmembrane protein Vangl2 participates in critical hippocampal-dependent memory processes in adult mice by modulating DG granule cell connectivity. Here, using an early conditional vangl2 knock-out (EMX1 cKO) mice, we show that Vangl2 also participates in shaping the DG/CA3 synapse and associated functions. The protein is enriched in the stratum lucidum of the CA3 of the hippocampus as early as P7, and an early vangl2 deletion strongly delays synaptic morphogenesis. Using Serial Block-Face Scanning Electron Microscopy (SBF-SEM) we show that in absence of vangl2 the size and complexity of the normally large mossy fiber bouton/thorny excrescences (MfB/TE) synapses are severely reduced, while PSDs number is reduced. At the same stage the synaptic properties of these abnormally small synapses are also disrupted. Using whole-cell voltage-clamp recordings, we first looked at spontaneous excitatory postsynaptic currents (sEPSC). We observed that both amplitudes and frequencies of sEPSC events are decreased in EMX1 cKO mice synapses, suggesting that vangl2 deletion affects both pre- and postsynaptic compartments. We next investigated whether the strength of synaptic transmission is affected in these synapses through AMPA/Kainate and NMDA EPSCs recordings. Unexpectedly, the AMPA/NMDA ratio was unchanged in absence of Vangl2 suggesting that the postsynaptic compartment is unaffected. We next analysed the presynaptic function using paired pulse ratio (PPR) and 20Hz stimulation trains. The PPR showed a reduced ratio of EPSCs in EMX1 cKO mice for shorter stimuli intervals (25 ms and 50 ms). Next we applied 20Hz train of stimulation, and observed that presynaptic facilitation is nearly abolished in EMX1 cKO mice. These results are consistent with a presynaptic compartment deficits in absence of Vangl2. Altogether our results suggest that the core PCP protein Vangl2 controls the structural development and function of the MfB/TE synapse, and is notably important for the maturation of the presynaptic compartment.
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NeurosciencesOrigine | Fichiers produits par l'(les) auteur(s) |
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