Cours: Synapses and Transmission

Synapse Formation

• Synapse formation involves the coordinated assembly of presynaptic and postsynaptic components.
• Presynaptic components include synaptic vesicles, active zone proteins (e.g., Bassoon, Piccolo), and neurotransmitter transporters.
• Postsynaptic components include specialized receptors and scaffolding proteins (e.g., PSD-95, Gephyrin).
• Active zone assembly can occur independently of a postsynaptic partner.
• Synaptogenesis is influenced by factors like contact with the postsynaptic partner and delivery as preassembled units or single components.
• Vesicle fusion, active zone, and postsynaptic density (PSD) are crucial components in synapse formation.
• Proteins like SNAREs (e.g., syntaxin, synaptobrevin, SNAP-25) play a critical role in vesicle fusion.
• Synaptic vesicles contain neurotransmitters, which are released into the synaptic cleft upon stimulation.
• The speed of synaptic transmission is less than 1 millisecond.
• The rate of synaptic transmission is greater than 1 kilohertz.
• Synaptic dynamics exhibit a range of 10^6 fold change in neurotransmitter release rate.
• FRET (Förster/Fluorescence Resonance Energy Transfer) can probe intermolecular distances.
• FM1-43 can be used to study exocytosis by probing active zone assembly.
• Synapses in invertebrates or developing organisms exhibit features similar in function or structure to those found in mature vertebrates.

Evolutionary Development of Synapses

• Synapses and neural systems may have evolved more than once.
• Placozoa possess synaptic genes but lack synapses, suggesting a different evolutionary path compared to other animal phyla.
• Evolution of synapsis in Placozoa involves exocytosis and paracrine signaling in peptidergic cells, without neuronal or synaptic structures.
• Synapse evolution demonstrates a gradual development of neuronal gene expression programs.
• Synaptic development follows progressive steps from early life forms to more complex organisms, from absence of neurons to more refined structure and function.
• Specific genes (e.g., dsyd-1, dliprin-a) are essential for synapse formation in Drosophila.
• Drosophila melanogaster is a useful model system for studying synapse formation.
• Genetic interactions and biochemical interactions (eg., LAR-type receptors and calcium channel interactions) are key to synapse development in both Drosophila and C. elegans.
• Core active zone proteins (e.g., Piccolo, Bassoon, Neurexin) have conserved roles even across different species, indicating a degree of evolutionary continuity in fundamental synaptic functions.
• The small GTPase Rab3 is vital for normal active zone distribution and pre/post matching.
• Synaptic formation in various species displays differences in the specifics of involved genes but shared fundamental principles of development.

Ontogenetic Synapse Formation

• Ontogenetic synapse formation refers to synapse formation during development.
• Ontogenetic synapse formation involves interactions between presynaptic and postsynaptic elements, leading to specialized structures and functions.
• Synapse formation is a complex process, requiring the coordination of different molecular and cellular mechanisms.

Additional Notes

• Neuroligin expression in non-neuronal cells directs clusters involving glutamate- and GABA-containing synaptic vesicles in mice.
• Questions remain about whether contact with the postsynaptic partner is necessary for synapse formation and whether synapses form from preassembled components or individual components.
• The delivery of active zone components (e.g., Bassoon, Piccolo) and synaptic vesicle proteins (e.g., VAMP, SV2) follows a preassembled multi-vesicle transport vesicle model.
• Partial axonal co-transport of active zone and synaptic vesicle proteins in presynaptic lysosome-related vesicles (PLVs), particularly requiring Arl8 lysosomal kinesin adaptor.
• Microtubule polarity guides synaptic component transport towards synapse formation sites.
• Assembly mechanisms and delivery methods for the formation of functional synapses are still to be fully elucidated.