α-Synuclein-Based Animal Models of Parkinson's Disease: Challenges and Opportunities in a New Era.

In recent years, a new generation of animal models of Parkinson's disease (PD) based on ectopic expression, overexpression, or intracerebral injection of the protein α-synuclein have emerged. Critically, these models develop inclusions of aggregated α-synuclein and/or α-synuclein-mediated neuronal loss replicating the defining pathological hallmarks of PD and driving significant advances in the understanding of the pathogenic mechanisms underpinning PD. Here, we provide a comprehensive review of this new generation of animal models of PD, ranging from invertebrate to rodent to nonhuman primate.

The Nanophysiology of Fast Transmitter Release.

Action potentials invading the presynaptic terminal trigger discharge of docked synaptic vesicles (SVs) by opening voltage-dependent calcium channels (CaVs) and admitting calcium ions (Ca(2+)), which diffuse to, and activate, SV sensors. At most synapses, SV sensors and CaVs are sufficiently close that release is gated by individual CaV Ca(2+) nanodomains centered on the channel mouth. Other synapses gate SV release with extensive Ca(2+) microdomains summed from many, more distant CaVs.