Optogenetic modulation of calcium channel dynamics in the presynaptic membrane

In the brain, information transfer and processing depend on the interplay of neuronal networks and is critically regulated by the function and plasticity of even single synapses. In chemical synapses, the action and molecular organization of voltage-gated calcium channels (VGCCs) is critical to initiate the vesicular release of neurotransmitters and thus allows information transfer. This work addresses the molecular basis of synaptic transmission from the view of presynaptic VGCCs organization and surface dynamics. Using a combination of immunocytochemistry, high-resolution optical methods, and electrophysiology it demonstrates the meaning of VGGC's alternative splicing for synaptic release probability and short-term plasticity. Applying an optical approach to acutely interfere with the intrinsic surface mobility of VGGCs provides a new concept of the flexible association between presynaptic calcium channels and synaptic vesicles as the basis for synaptic short-term plasticity. The outlook gives an idea about future applications of the gained molecular insights as well as the created optical tool for subsequent projects in the both, the calcium channel field and the general field of synaptic physiology.