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Glycine/GABA mixed inhibitory synapses studied with super-resolution microscopy : differential regulation of GlyRs and GABAARs by excitatory activity

Abstract : Stochastic optical reconstruction microscopy (STORM) bypasses the diffraction limit by recording spatially and temporally separated single molecule signals, achieving a resolution of ~10-40 nm. In my study, I have developed a two-color dSTORM imaging and data analysis strategy, in order to investigate the ultrastructure of mixed inhibitory synapses. My results show that GlyRs, GABAARs, gephyrin and RIM1/2 exhibit a heterogeneous intra-synaptic organization and form sub-synaptic domains (SSDs). GlyRs and GABAARs were not fully intermingled, but sometimes occupied different spaces at the post-synaptic density (PSD). In addition, post-synaptic gephyrin SSDs were aligned with pre-synaptic RIM1/2 SSDs, forming trans-synaptic nanocolumns. During elevated neuronal activity by 4-AP treatment, the spatial correlation between GlyRs, GABAARs and gephyrin was increased at the PSD. Moreover, the spatial correlation of GlyRs and RIM1/2 was also increased, while that of GABAARs and RIM1/2 did not change. The number of SSDs per synapse for these synaptic proteins was not changed by 4-AP. My study thus provides a new angle for understanding the mechanisms underlying GABAergic/glycinergic co-transmission.
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Submitted on : Wednesday, November 6, 2019 - 2:47:18 PM
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Xiaojuan Yang. Glycine/GABA mixed inhibitory synapses studied with super-resolution microscopy : differential regulation of GlyRs and GABAARs by excitatory activity. Neurons and Cognition [q-bio.NC]. Université Paris sciences et lettres; East China normal university (Shanghai), 2019. English. ⟨NNT : 2019PSLEE012⟩. ⟨tel-02351605⟩

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