Memory strength dependent on abundance of ‘package’ deliveries

The research, conducted using fruit flies as model organisms, focused on dopamine neurons. It was published online in the journal Neuron. “The aim of this project was to figure out the mechanistic changes that can lead to constraints in learning and memory,” says first author Anna Phan, PhD, a postdoctoral researcher in the lab of senior author Ron Davis, PhD, a professor in the Department of Neuroscience at Scripps Research in Jupiter, Florida. Unexpectedly, the team also found that having a good or poor memory may be determined early in life. “These changes occur at a very specific time during development, but not in adulthood,” Phan explains. The researchers focused on a protein called stromalin. Earlier research by the Davis lab identified stromalin as one of several proteins that act as a memory suppressor. That is, it seems to constrain memory formation when working normally. If the ability to make stromalin is knocked out in the fruit flies, memory is enhanced, Davis says. But until now, how this protein functions to regulate memory formation was not known. In the current study, the investigators used a number of laboratory tools, including high-resolution imaging techniques, to determine the alterations that lead to the suppression—and enhancement—of memory. After ruling out changes in the form of the neurons or in their numbers, they eventually determined that knocking out the gene for stromalin had one very striking effect: It increased the number of the neurotransmitter vesicles, or “packages,” that transfer information from dopamine neurons onto their downstream partners. “This strengthens the communication at the synapses,” Phan says. “Our studies indicate that this is what leads to the memory enhancement that we see.” Stromalin has many other functions. These include helping chromosomes find their way during cell division and regulating the expression of genes. The protein has been evolutionarily conserved from yeast all the way to humans, Phan says. Understanding stromalin’s normal role in suppressing learning and memory is important, she says. There are good reasons why memory may need to be constrained. “Unconstrained memory is like a car without brakes,” Phan says. “If it’s the only car on the road, maybe you can get away with it. But in reality, there are multiple other cars trying to get to where they’re going. You can think of the cars like different kinds of neural signals, controlling a variety of critical functions in the body. Without a way to regulate the system, you end up with a big mess and mass confusion.” In fact, mutations in the stromalin gene can lead to seizures, hyperactivity, and autistic behaviors, in addition to other, non-neurological problems, Phan says. The next step will be identifying drugs that act on this type of synaptic signaling, she says. Ultimately, the discovery may offer a new path for developing treatments for Parkinson’s disease, which also results from defects in the dopamine neurons, as well as therapies to improve learning and memory, Davis says. “Our studies open an entrée into studying the cell biology of the neuron that was previously unrecognized,” Davis says. “Stromalin seems to be the first identified protein that controls the number of synaptic vesicles in neurons without altering the number of synapses between neurons. It shows that the number of synaptic vesicles that form is controlled independently from synapse number.” Other contributors to this paper, Stromalin Constrains Memory Acquisition by Developmentally Limiting Synaptic Vesicle Pool Size, were Scripps Research investigators Molee Chakraborty and Jacob Berry. Connon Thomas and Naomi Kamasawa of the Max Planck Florida Institute were also contributors. This study was supported by the National Institutes of Health (grants 5R37NS019904, 2R01NS052351, and 1R35NS097224) and a Canadian Institutes of Health Research postdoctoral fellowship. About Scripps Research Scripps Research is ranked the most influential scientific institution in the world for its impact on innovation. A nonprofit research organization, Scripps Research expands basic knowledge in the biosciences and uses these fundamental advancements to develop profound innovations that improve well-being. Scripps researchers lead breakthrough studies that address the world’s most pressing health concerns, accelerating the creation and delivery of medical breakthroughs to better human health across the globe. Our educational and training programs mold talented and committed students and postdocs into the next generation of leading scientists. Media contact: Stacey Singer DeLoye, sdeloye@scripps.edu, (561) 228-2551 Once posted online, all releases can be accessed through Scripps Research News & Events.