Our brains are marvels of connectivity, packed with cells that continually communicate with one another. This communication occurs across synapses, the transit points where chemicals called neurotransmitters leap from one neuron to another, allowing us to think, to learn, and to remember.
Researchers have known that these synapses often need a boost to send information across neuronal divides. But where that boost comes from has been a mystery.
Now HMS researchers have discovered a gene that gives that boost by increasing neurotransmitter release in a phenomenon known as synaptic facilitation. They discovered this by turning on a light or two.
The gene is synaptotagmin 7 (SYT7), a calcium sensor that dynamically increases neurotransmitter release; each release serves to strengthen communication between neurons for about a second.
These swift releases are thought to be critical for the brain’s ability to perform computations involved in short-term memory, spatial navigation, and sensory perception.
The team of researchers that made this discovery was led by Skyler Jackman, a postdoctoral researcher in the lab of Wade Regehr, an HMS professor of neurobiology. They reported their findings online January 6 in Nature.
A dozen years ago, Regehr suspected that SYT7 might drive the synaptic strengthening process: The gene turns on slowly and then ramps up in speed, which would fit gradual release of neurotransmitters.
Jackman furthered this thinking by refining the way of assessing the role of SYT7; he tested synaptic connections in brain tissue taken from mice that lacked the SYT7 gene but still had intact brain circuits, an experiment more reflective of how neurons and synapses might work in a living animal.
“The results were striking,” Jackman says. “As soon as we probed these connections we found a huge deficit, a complete lack of synaptic facilitation in the knockout mice, completely different from their wild-type brothers and sisters.”
To verify that SYT7 was responsible for this change, Jackman found a way to reinsert SYT7 and then restore its function on demand. He did this by using two techniques: optogenetics, a genetic manipulation tool that allows neuronal connections to be turned on and off with light; and bicistronic expression, a method that packages one optogenetic protein and one SYT7 protein into a single virus that infects all neurons equally. Using these two techniques, Jackman could selectively study what happened when SYT7 was reinserted into a neuron and measure its effects reliably.
Jackman wants to use these techniques to study subsets of neurons in different parts of the brain to see whether the gene affects fear in the amygdala, for example, or spatial navigation in the hippocampus.
Image: Regehr lab