Chemical Biology, Neuroscience
Janelia Research Campus
Dr. Sternson is a group leader at the Janelia Research Campus.
The Neurobiology of Need
How does the brain encode motivations? Why do we do what we do? Scott Sternson is trying to address these questions by looking at the origins of our most fundamental motivations –behaviors, such as hunger and thirst, that are physiologically imperative for survival. To decipher the neurobiology of these survival needs, his lab group uses a combination of advanced molecular and systems neuroscience approaches.
Ultimately, Sternson would like to understand how neural circuits mediate flexible, goal-directed behaviors. He focuses on circuits for specific survival needs that are under strong selective pressure. Nevertheless, satisfying these needs requires an organism to demonstrate flexible behaviors in a complex and dynamic environment. To simplify the complexity of this problem, Sternson’s team starts from small sets of specialized neurons whose activity is sufficient to trick the brain into thinking it’s in a state of physiological need. This enables the team to take a reductionist approach to elucidate circuits, neuronal computations, and motivational principles associated with physiological need states.
The primary focus of Sternson’s lab is on neurons that induce hunger. His team’s work starts in the hypothalamus and looks at its interactions with a variety of other brain areas. They have also developed many tools, especially chemogenetic tools, for investigating cell types in different brain areas. Currently, his group looks at cell type specification using RNA-Seq and cell-type-specific neural circuit function using opto/chemogenetics. They also use deep-brain calcium imaging to understand neuronal dynamics in appetite circuits. All of these technical approaches are applied in the context of behavioral paradigms and designed to deconstruct the motivational properties of need-sensing neurons.
An important challenge in neurobiology is understanding how the brain gives rise to our motivations. Scott Sternson arrived at the Janelia Research Campus in 2007, wanting to study the neural basis of motivation. In other words, why we do what we do. He’s been finding answers by focusing on hunger, one of the most fundamental and insistent motivations that animals must satisfy. By identifying brain circuits that mediate hunger, Sternson’s team is illuminating mechanisms that might also explain how the brain establishes other motivational states.
Trained as a chemist before delving into neuroscience as a postdoctoral researcher, Sternson says he still retains a chemist’s mindset, approaching his research by searching for fundamental rules that can be used to explain complex processes. His findings so far are exciting because they suggest that simple principles may underlie seemingly complex motivations.
The explorations of hunger circuitry in his lab began with a set of cells already known to regulate body weight: the AGRP neurons in the brain’s hypothalamus. Sternson’s team found that they could “hack the hunger system” by artificially activating AGRP neurons. This was all it took to drive an animal – even a well-fed one – to eat voraciously. And when they switched off the neurons, the animal would stop eating. This capability set his team up for broader explorations of the system’s underlying circuitry.
Sternson has found that AGRP neurons provoke an animal to eat by inducing an unpleasant sensation that persists until food is consumed. “Instead of controlling feeding behavior directly, these neurons have a very unique teaching function,” he says. “The animal comes to learn that, when these neurons are active, to turn off this unpleasant internal state you eat.” Although everyone knows hunger is uncomfortable, no one had found the cells that are responsible for this feeling.
“Even though hunger and food-seeking behaviors can look very complex, it appears that these learned behaviors result in part from a surprisingly simple principle where animals are just trying to minimize the output of these neurons,” he says. Sternson went on to show that separate thirst-sensitive neurons act in a similar way, creating an unpleasant sensation that drives an animal to drink. He suspects the same mechanism may also guide behaviors that ensure animals meet other needs.
Sternson believes that a better understanding of our most basic motivations, such as hunger and thirst, will lay down a foundation for understanding the neural processes underlying more complex motivations in the future.