Arnaldo Carreira-Rosario Wants to Understand How Brains Power Up
September 14, 2023 | By Marie Claire Chelini
Originally published by Duke Department of Biology
You just bought a brand-new, top-notch computer. You take it out of the box and press the power button, anxious to get it going. The machine purrs slightly, the display lights up, and then you wait five, 10, maybe even 15 minutes until the whole thing boots up.
Using Drosophila fruit flies as a study system, Carreira-Rosario looks at what happens to the nervous system while an embryo develops, investigating how the brain goes from an inactive little bundle of tissues to a fired-up powerhouse of activity.
To that end, he looks at each individual neuron. Which one gets activated first? What follows it? And what happens if you force things to happen in a different order?
“It doesn't seem to be random,” Carreira-Rosario says. “When you turn on a computer, software gets uploaded in a specific order. The brain does a similar thing. Specific neurons, specific parts of the brain, need to be turned on in a specific order for the nervous system to work properly.”
He describes one of his recent findings: It was well-known that muscles can start twitching during an animal’s embryonic development before the nervous system becomes active. By looking closely at fruit fly embryos, Carreira-Rosario noticed that these muscle twitches were accompanied by a little bit of activity from sensory neurons. The muscles twitches could therefore be a trigger, necessary for the rest of the nervous system to boot up.
By selectively blocking the neuron activation, Carreira-Rosario found that the opposite is true: inhibiting the neurons responsible for sensing muscle twitches — as well as blocking the muscle twitches themselves — leads to an expedited activation of the rest of the nervous system. These neurons, thought of as triggers, are more likely to be brakes.
“How is it that these muscle contractions, early on, before the nervous system activates, are telling the nervous system when to get started?” he wonders. “Normally it’s the other way: The nervous system tells the muscles what to do.
“In this case, it looks like the muscles are the ones telling the nervous system when to start. What is the circuitry, within the nervous system, that is controlling the timing for when the nervous system is going to become active?”
Another focus of his research deals with the long-term consequences of events happening during brain activation.
“This initial activity of the brain has a permanent influence on how the brain functions later on,” Carreira-Rosario says. He mentions the importance of “critical periods.” “You know, when we're very young, we learn how to speak different languages very easily. If you want to start to learn a new language in your 20s, it gets harder and harder.
“These critical periods correlate with when the nervous system is still developing. So different changes during this period can have effects that will last for the life of the organism,” Carreira-Rosario says.
To take such a close look into the brain of a fruit fly embryo, Carreira-Rosario uses a technique called fluorescent imaging. He manipulates fruit fly embryos, “tagging” their genetic code with a protein that shines brightly whenever neurons get activated — just like those indicator lights that tell you your appliance has been plugged in. By observing the embryos develop under a specialized microscope, he can then see the exact moment in which different neurons become active.
Carreira-Rosario became interested in the “how” behind things as an undergraduate student in his native Puerto Rico. Originally aiming at a job in the pharmaceutical industry, he took a sideways door to an immunology lab and fell in love with hypothesis-driven research. Fruit flies entered the picture during his Ph.D. at the University of Texas Southwestern, and a prestigious K99 grant from the National Institute of Health allowed him to push the boundaries of fruit fly neurobiology as a postdoctoral researcher at Stanford University.
Now in Durham, he is ready to push these boundaries even further. He’d also like to find a soccer team to join, as well as good mountain bike trails to explore. If the weather allows it, of course.
Indeed, one of the unintended and nonacademic consequences of his time in Northern California is that, until his arrival in Durham, humid heat was a distant memory. “I lost the habit!” he laughed.