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Prizewinner’s Research Reveals How Aggressive Motivation Is Regulated in Mouse Brain

photo of Ann Kennedy leaning on railing

Ann Kennedy is the winner of the 2022 Eppendorf & Science Prize for Neurobiology for research that provides new insight into aggression and how aggressive motivation is regulated by the mouse brain.

Kennedy's prize-winning work shows how neuronal activity in the hypothalamus can fine-tune core animal behaviors, controlling them like a volume knob, rather than an all-or-nothing switch.

The annual prize recognizes the important role of neurobiology in advancing the understanding of the functioning of the brain and nervous system. The winner receives $25,000 and publication of their essay in the November 4 issue of Science.

Although it can take many forms, aggression exists in many animal species. It's an evolutionary ancient behavior crucial to the survival of a species. But engaging in a fight can be costly to an individual as even the winners can walk away with serious injuries.

Thus, it is common — and safer — to begin a conflict with threat displays and posturing, and attack only if necessary. This type of aggressive arousal is an archetypal motivational state that exhibits persistence and graded intensity; it builds and maintains until the threat or the need to intimidate is gone.

Although previous research has shown that the ventrolateral portion of the ventromedial hypothalamus (VMHvl) is implicated in control of aggression in mice, the underlying mechanisms are unknown.

"There's been decades of work in neuroscience studying sensory processing or motor actions, but we know much less about what happens in between how we decide what to do about the world we encounter," said Kennedy, an assistant professor at Northwestern University Feinberg School of Medicine.

To better understand how this works, Kennedy and her colleagues used head-mounted miniaturized microendoscopes to characterize the activity of neurons in this region as mice freely interacted.

While the researchers found that activity in VMHvl neurons was only weakly correlated with when mice engage in a fight, they revealed that a small population of these neurons was persistently active over the duration of a social encounter with another mouse with modest fluctuation in the intensity of their activity as the animals interacted with one another in different ways.

When this patterning was weak, mice simply investigated or ignored each other, but as the patterning grew in intensity, so did aggressive posturing behaviors, including actions like dominance mounting. When neuron activity hit its peak, animals began to exhibit outright attacks.

Kennedy suggests that this signal reflects a level of aggressive motivation and argues that the scalable and persistent activity within the VMHvl is a mechanism for setting an animal's motivational state.

"The findings help us understand how the brain maintains motivational states," said Kennedy. "If a mouse sees a predator or gets in a fight, it doesn't forget about it right away. The heightened arousal hangs around and modifies the way it behaves."

The neuronal population discovered is correlated with an animal's will to fight, rather than the act of fighting itself. The findings support the idea that these neurons play a role in setting the high-level motivational state of the animal.

"[The finding] also gives us a new or different way of thinking about how the brain keeps track of the high-level motivations that shape our moment-to-moment behavior," said Kennedy.

"It paints a picture of the brain as a hierarchical controller, with hypothalamic regions setting overall motivations which other regions then act upon to generate specific motivated actions."

"Since 2002 Eppendorf has partnered with the prestigious journal Science to create what the prize has become today, one of the leading awards for young scientists in neurobiological research," said Eva van Pelt, Co-CEO of Eppendorf SE. "Congratulations to [Dr.] Kennedy on her fantastic achievement in winning this year's prize."

2022 Finalists

Kevin Guttenplan headshot
Kevin Guttenplan | Aaron Bielek

Kevin Guttenplan for his essay, "Why do neurons die." Guttenplan received his undergraduate degree in neuroscience and mathematics from Pomona College and a Ph.D. from Stanford University, where he worked in the laboratories of Ben Barres and Aaron Gitler, studying the role of astrocytes in disease and injuries of the nervous system. He is now a Helen Hay Whitney postdoctoral fellow in the laboratory of Marc Freeman in the Vollum Institute at Oregon Health and Science University, studying the role of astrocytes in neuronal circuits.

Filipa Cardoso for her essay, "The brain fat connection." Cardoso received her bachelor's degree in biochemistry and master's degree in health sciences from Universidade do Minho, where she was introduced to the field of immunology, working on the immune response to tuberculosis infection and to colitis models.

Filipa Cardoso headshot
Filipa Cardoso

After her master's, she moved for a Ph.D. in Henrique Veiga-Fernandes' laboratory to develop research on how the nervous and the immune systems interact to control metabolism. After completing her Ph.D., Cardoso joined a biopharmaceutical company, LIMM Therapeutics, which stemmed from the Veiga-Fernandes laboratory. Cardoso's current research strives to translate the knowledge obtained from basic research to clinical application by harnessing the molecular crosstalk between neuronal and innate lymphoid cells within peripheral tissues.