Different states of synaptic vesicle priming explain target cell type-dependent differences in neurotransmitter release.

Pronounced differences in neurotransmitter release from a given presynaptic neuron, depending on the synaptic target, are among the most intriguing features of cortical networks. Hippocampal pyramidal cells (PCs) release glutamate with low probability to somatostatin expressing oriens-lacunosum-moleculare (O-LM) interneurons (INs), and the postsynaptic responses show robust short-term facilitation, whereas the release from the same presynaptic axons onto fast-spiking INs (FSINs) is ~10-fold higher and the excitatory postsynaptic currents (EPSCs) display depression. The mechanisms underlying these vastly different synaptic behaviors have not been conclusively identified.

Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion.

The presynaptic SNARE-complex regulator complexin (Cplx) enhances the fusogenicity of primed synaptic vesicles (SVs). Consequently, Cplx deletion impairs action potential-evoked transmitter release. Conversely, though, Cplx loss enhances spontaneous and delayed asynchronous release at certain synapse types.

Interpretation of presynaptic phenotypes of synaptic plasticity in terms of a two-step priming process.

Studies on synaptic proteins involved in neurotransmitter release often aim at distinguishing between their roles in vesicle priming (the docking of synaptic vesicles to the plasma membrane and the assembly of a release machinery) as opposed to the process of vesicle fusion. This has traditionally been done by estimating two parameters, the size of the pool of fusion-competent vesicles (the readily releasable pool, RRP) and the probability that such vesicles are released by an action potential, with the aim of determining how these parameters are affected by molecular perturbations. Here, it is argued that the assumption of a homogeneous RRP may be too simplistic and may blur the distinction between vesicle priming and fusion.

Fully-primed slowly-recovering vesicles mediate presynaptic LTP at neocortical neurons.

Pre- and postsynaptic forms of long-term potentiation (LTP) are candidate synaptic mechanisms underlying learning and memory. At layer 5 pyramidal neurons, LTP increases the initial synaptic strength but also short-term depression during high-frequency transmission. This classical form of presynaptic LTP has been referred to as redistribution of synaptic efficacy.