Of Signals and Neurons

Initially, Amber L. Alhadeff had planned to become a doctor. As the time of enrollment came closer, she thought about possible prerequisites. A little research perhaps? She then leafed through the directory of her university in Pennsylvania and sent a very brief message to a guy named Harvey Grill: “Do you need help? Count me in!” Who could have guessed that this would turn out to be the start of her academic career? “Within a few months, I turned all my career plans upside down”, she laughs in retrospect. While today she holds a doctorate degree, her passion no longer lies with medicine.
It is worth knowing that her mentor, Dr. Harvey Grill, is not just anyone, but rather a renowned neuroscientist who studies complex connections between the brain and eating habits. As a young student, who was 18 years old at the time, she was fascinated by the subject matter, but also by the way of working and exchanging ideas within a research team: “Where else can you combine curiosity and creativity in such a wonderful way?” This being a rhetorical question, Alhadeff has nonetheless remained faithful to scientific research – for 15 years and counting!

Food intake screened
Food, she tells us during the call, is the one true constant in her life. Her family celebrates food and eating. Every evening, the family dined together, without exception. And on the weekends, with the grandparents, dining became a feast. It implies social exchange, pleasure and joy. Later, in college, it took on an entirely new meaning. She started running – long-distance running. Food was now checked for certain fitness criteria. Nutrition and metabolism: as an athlete, she began looking at nutrition from a theoretical perspective. A rather profitable alliance: she finished her last marathon in 3:22.
Today, Amber L. Alhadeff is not only 15 years older; the 33-year-old is a highly successful neuroscientist, and on the topic of eating, she is more than capable of serving a number of new ingredients which spring from her own research. Food has been promoted to be her professional main course, or, as she describes it, “My personal life is reflected in my professional life.” She recently published the results of her research into hunger-sensitive neurons in the brain and the ways in which they communicate with signals from the gastro-intestinal tract, as well as influence survival strategies, in the journal “Science”. For this work, the Principal Investigator was awarded the 2021 “Eppendorf & Science Prize for Neurobiology”, worth $25,000. Welcome recognition indeed as she starts her own laboratory at the Monell Chemical Senses Center in Philadelphia, which she has been heading for two years now – having opened it a mere three months before the pandemic struck.

When the stomach growls
“One cannot think well, love well, sleep well, if one has not dined well.” This quote is featured on her carefully designed website. It originated from the writings of Virginia Woolf – but it could just as easily have been penned by Amber L. Alhadeff. After all, it touches the core of her scientific questions: why do we feel different when our stomachs growl? Nervous. Unsettled. A bit off. “Hunger”, says the researcher, “definitely alters our perception.” In her “Science” essay, she writes about her research: “I wanted to connect the brain networks governing hunger with other signals in the body.”

The sensation of hunger originates in the brain – in the hypothalamus, to be exact. This is where many signals converge, and where hormones can be released. However, Alhadeff and her team are also interested in finding out “whether there are neurons that code for hunger and thus possibly modify other behaviors”. And what is the actual role of the reward system in the brain? How are the homeostatic, i.e., the metabolism-dependent signals connected with one another? She observes mice to find out how this information from the interior of the body influences brain activity.
The young scientist is grateful for state-of-the-art technology. The mice can move freely while specific fiberoptic cables, or miniature microscopes, illuminate their interiors and thus transmit hitherto undetected nutrient signaling pathways to monitors and scans.

Open for new avenues
Absolutely – science is her dream job; she can’t imagine doing anything else. But it is not an easy profession. Her desk is a mess, with papers over here and more piles over there. She understands that one must remain flexible and should not focus too hard on one specific topic from the outset. The first of her two discoveries was practically the product of chance. While studying to find out how hunger codes in the regions of the brain, she realized: “Those who are hungry will also experience pain.” And she asked herself: what will happen if one is also injured, or if inflammation ravages the body? “How will the brain tell us what is more important – hunger or pain?”
It is precisely this process that Alhadeff and her team were able to investigate. The result: extreme hunger can displace the perception of pain caused by injury or inflammation. The mice ignored the inflicted pain and secured their survival by searching for food. Alhadeff finds this “mega-exciting”, and she can imagine that additional research could contribute to, for instance, conquering the serious problem of opioid abuse in the US.

Why do fat and sugar reward us?
The second discovery concerns the signaling pathways inside the body. Alhadeff’s team discovered a hitherto brain-gut connection. If the mice received fat through a catheter leading to their stomachs, the fat signals were transmitted to the brain via the vagus nerve. Sugar, on the other hand, utilizes neurons in the spinal cord – afferent cells – to communicate with the hunger-neurons in the hypothalamus. The question is not what is better; rather, the award-winning scientist speculates that this might explain why foods that contain both fat and sugar are especially adept at activating our reward system inside the brain. With obesity being another serious problem, Alhadeff once again takes the broader picture into account.
Something else is important to her: cultivating a more inclusive culture within the harsh reality of science; and promoting women, as well as all others who would otherwise fall through the cracks due to their race, ethnicity, sexuality, or their socio-economic background. The job is challenging; it takes many different perspectives for innovation and for scientific advancement – not only the mainstream view.

Off the Bench magazine 02 I 2022