How Fast Do Your Nerve Cells Talk?
Madison, Wisconsin - Sometimes you just have to build your own.
Researchers at the University of Wisconsin School of Medicine and Public Health were interested in seeing how different members of a family of proteins affect the speed of electrical signals passed from one brain cell to the next.
The change in speed affects the rate at which neurons talk to each other, which likely has implications in how entire ‘circuits’ of cells communicate.
So they did a little engineering. Normally, neuron-to-neuron communication is controlled by members of the synaptotagmin protein family. The proteins are attached to vesicles—small bundles in the neuron that contain neurotransmitters—and help the vesicle release its cargo into the synapse, transmitting a signal to another cell.
The speed of this release determines, among other things, how quickly and how strongly the receiving neuron can respond to the next wave of signals.
Two recent papers describe how researchers engineered chimeras, proteins built in a cut-and-paste fashion from two existing proteins, to “tune” the speed of neurotransmitter release. One study used parts from the fastest and slowest members of the Synaptotagmin family (syt1 and syt7).
The work was conducted by UW-Madison graduate students Chantell Evans, who performed the biochemistry, and David Ruhl, who performed the experiments in cells. A second study, performed by postdoctoral fellows Renhao Xue and Jon Gaffaney, used syt1 and a calcium-binding protein found in the brain and other various tissues, Doc2B.
To measure the speed (or kinetics) of neuron-to-neuron communication, the researchers grew brain cells in dishes, stimulated individual neurons, and recorded the electrical current as it flows into the receiving neuron over time.
One neuron firing looks somewhat like a heart monitor measuring a heartbeat, but with only one very fast spike in activity and a decaying tail with an exponential curve. But with the chimeras, the spike of activity was slower to reach its pinnacle and the tail took longer to return to a resting state as well.
“When we put these chimeras into neurons, it slowed the rise of the postsynaptic currents and it also slowed their decays,” said Ed Chapman, a Howard Hughes Medical Institute investigator and professor of neuroscience in the School of Medicine and Public Health. “We were able to change the speed of the synapse by changing the intrinsic speed of the calcium sensor that drives vesicle exocytosis.”
The rate of that decay is a big deal, as it underlies the ability of neuronal circuits to “reverberate,” that is, to continue to signal one-another for a prolonged period of time, and this is thought to mediate certain forms of short-term memory. By changing the speed of the synaptic decays, Chapman and co-workers can now conduct experiments to determine the rules that underlie reverberation.
Going forward, the Chapman lab is taking its electrophysiology work down the hall to Bob Pearce, chair of anesthesiology at the School of Medicine and Public Health, to put these chimeras into the brains of mice to examine their effects on the function of an entire network, and ultimately to look at differences in cognition and behavior.
These two studies, “Structural elements that underlie Doc2B function during asynchronous synaptic transmission” and “An engineered metal sensor tunes the kinetics of synaptic transmission,” were published in the Proceedings of the National Academy of Sciences (PNAS)-Plus – Neuroscience on July 20, 2015, and the Journal of Neuroscience on August 26, 2015, respectively.
An image from the UW-Madison study published in the Journal of Neuroscience also graces the cover of the journal, showing a confocal image of a cultured hippocampal neuron from a synaptotagmin-1 knock-out mouse.
Date Published: 08/26/2015