Behind all motor, sensory and memory functions, calcium ions are in the brain, making those functions possible. Yet neuroscientists do not entirely understand how fast calcium ions reach their targets inside neurons, and how that timing changes neural signaling. Researchers at the Okinawa Institute of Science and Technology Graduate University have determined how the distance from calcium channels to calcium sensors on vesicles affects a neuron’s signaling precision and efficacy. In international collaboration with research institutes such as the Pasteur Institute and the Institute of Science and Technology Austria, Professor Tomoyuki Takahashi and the Cellular and Molecular Synaptic Function Unit described the locations of voltage-gated calcium channels, which allow calcium ions to enter into the neuron, triggering vesicles to release neurotransmitters, signaling to the next neuron. This research, to be published in the January 7, 2015 issue of Neuron, illuminates decades of mystery behind the precision and efficacy of neurotransmitter release, suggesting how signaling changes as an animal matures.
After an electrical spike, or an instantaneous change in voltage, travels through the neuron, it reaches the presynaptic terminal. The presynaptic terminal is an area facing the synaptic cleft, or the gap between one neuron and the next. The electrical spike triggers voltage-gated calcium channels to open, allowing calcium ions to enter the presynaptic terminal. The calcium ions then diffuse locally around the channels and encounter synaptic vesicles, small packages of neurotransmitters, which are signaling molecules. The calcium ions interact with sensor proteins on the vesicle, triggering the vesicles to fuse with the presynaptic terminal membrane, and releasing neurotransmitters into the synaptic cleft toward the next neuron.
This diagram shows the new model that Professor Takahashi and his collaborators have proposed. Circles are vesicles filled with blue neurotransmitters, and the smaller grey circles are voltage-gated channels. Instead of measuring from the vesicle to the center of the channel cluster (green line), Takahashi suggests measuring to the perimeter of the channel cluster (red line). The difference is that measuring to the center varies with the size of the cluster, whereas measuring to the perimeter will always describe the closest channel to the vesicle
Image credit: OIST
This work was supported by the Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency.