Antoine Triller

..In this primer, we will review the different approaches used to track single molecules in live neurons, compare them to bulk measurements, and discuss the different concepts that have emerged from their application to synaptic biology...

..These results indicate that SV docking at the plasma membrane and functional priming are respective morphological and physiological manifestations of the same molecular process mediated by SNARE complexes and Munc13s...

..This transient activity-dependent reduction of inhibition would favor the onset of LTP during conditioning...

..Since alterations in the oligomerization properties of gephyrin are related to the dynamics of GlyRs, the gephyrin splice variant ge(2,4,5) may be implicated in the modulation of synaptic strength...

..Consequently, GlyR number at synapses may be rapidly modulated by the cytoskeleton through the regulation of lateral diffusion in the plasma membrane and of receptor stabilization at synapses...

..This provides a mechanism for maintaining or adjusting the steady state of postsynaptic molecule exchanges and the level of glycinergic inhibition in response to neuron- and glia-derived signals or extracellular matrix remodeling...

..Within clusters, we identified two subpopulations of GlyR with distinct degrees of stabilization between receptors and scaffolding proteins...

..This provides a mechanism for a rapid homeostatic regulation of the inhibitory glycinergic component at mixed glycine-GABA synapses in response to increased NMDA excitatory transmission...

..Moreover, the action of the potassium channel blocker 4-aminopyridine and receptor antagonists indicate that the dynamics of postsynaptic gephyrin scaffolds are controlled by synaptic activity...

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..These data suggest that the relative expression level of cellular variants influence the overall oligomerization pattern of gephyrin and thus the turnover of synaptic GlyR...

..Altogether, our results reveal a microtubule-dependent polarized reorganization of chemoreceptors at the cell surface and suggest that this polarization serves as an amplification step in GABA gradient sensing by nerve GCs...

..This 3D analysis reveals the morphological constraints exerted by the presynaptic molecular scaffold. SVs are tightly interconnected in the axonal bouton, and this network is preferentially connected to the AZ...

..Thus, postsynaptic selection of coreleased fast transmitters is used in the CNS to increase the diversity of individual neuronal outputs and achieve target-specific signaling in mixed inhibitory networks...

..The experimental procedure described for neurons below takes about 45 min. This technique is applicable to various cultured cells...

..This review is part of the TINS Synaptic Connectivity series...

..Therefore, lipid composition and actin-dependent protein compaction regulate viscosity of the PSM and, consequently, the molecular flow in and out of synapses...

..We will finally review potential mechanisms underlying the development of GABAergic interneurons...

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..Single QD tracking is nevertheless a general method, suitable to study many transmembrane proteins...

..Particularly, filamentous projections were observed linking the PSD to the actin cytoskeleton. Thus, synaptic ultrastructure can be analysed under more realistic conditions following HPF...

..Finally, GlyR clusters could be detected at synaptic sites with the GABAA receptor gamma2 subunit and gephyrin, suggesting that mixed GABA/glycine synapses might exist in the hippocampus...

..Therefore, our data strongly suggest that some GlyR clusters are associated with gephyrin on their way to the cell surface and that this association increases the accumulation of GlyR at the plasma membrane...

..Constraints, limitations and future developments are discussed...

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..KARAP/DAP12 may thus alter microglial physiology and subsequently synaptic function and plasticity through a novel microglia-neuron interaction...

..We will briefly review here recent data on this mechanism, which ultimately tunes the number of receptors at synapses and therefore synaptic strength...

..The entry of GlyRs into the synapse by diffusion was observed and further confirmed by electron microscopy imaging of QD-tagged receptors...

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..elegans tissues by using postembedding immunogold labeling...

..Because Dlc-1 and Dlc-2 have been described as stoichiometric components of cytoplasmic dynein and myosin-Va complexes, our results suggest that motor proteins are involved in the subcellular localization of gephyrin...

..Furthermore, its cell expression pattern suggests that it may contribute to specialized cellular function in the rat CNS such as neuronal metabolism, neurotransmission, and control of brain amino acid homeostasis...

..These results suggest that the cytoplasmic tail of gB plays a role in maturation and transport and subsequently in axonal sorting in differentiated hippocampal neurons...

..Thus, otoferlin is essential for a late step of synaptic vesicle exocytosis and may act as the major Ca(2+) sensor triggering membrane fusion at the IHC ribbon synapse...

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..Thus, our data show that the process of developmental neuronal death triggered by microglia is similar to the elimination of pathogenic cells by the innate immune cells...

..TNFalpha is also likely to induce immediate and delayed prodeath effects in adult and pathological tissues. Data obtained in embryonic systems will thus help to develop new therapeutic approaches to pathological neuronal death in adults...

..Synaptic dysfunctions may be at the origin of cognitive impairments, however the link between prenatal inflammation and synaptic defects remains to be established...

..They also indicate that GABAergic neurotransmission does not compensate for defects in GlyR postsynaptic aggregation leading to spastic syndrome in C57BL/6J SPA mice...

..Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives...

..From these data, we conclude that GABA(A)Rs located on parallel fibers depolarize parallel fiber terminals beyond the threshold for Na+ channel activation and thereby induce glutamate release onto MLIs and Purkinje cells...

..Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially AD...