Fight or flight? It depends…
August 31, 2023
Our instinct to flee, freeze, or fight in the face of danger is hardwired in our brains. Still, how we respond to danger doesn’t only depend on the threat in front of our eyes. In this week’s issue of ScienceAdvances, researchers from the Farrow lab at Neuro-Electronics Research Flanders (NERF, empowered by imec, KU Leuven, and VIB) hone in on how a brain region called the superior colliculus integrates sensory information with contextual cues to respond appropriately to danger.
All animals are born with a collection of instinctive and stereotypic behaviors, including freezing or trying to escape when faced with danger. But just because these behaviors are instinctive, doesn’t mean they can’t be flexible, says prof. Karl Farrow (VIB, imec, KU Leuven).
“We know that an animal’s response to a threat like a predator can be affected by how an animal is feeling (are they hungry, hurt, or caring for their young?), as well as environmental conditions (is there somewhere to hide nearby?)—however, how all of this information is processed in the brain to generate a flexible instinctive response is still unclear.”
At Neuro-Electronics Research Flanders (NERF) in Leuven, prof. Karl Farrow leads a team of researchers focused on dissecting the lines of communication between what we see and how we respond. A brain area of particular interest is a small region in the midbrain called the superior colliculus—a name derived from the Latin ‘upper hill’.
Information relay by the superior colliculus
“The superior colliculus plays a crucial role in the processing of visual information and triggering of innate behaviors,” explains Norma Kühn, a postdoctoral researcher in Farrow’s team.
Next to essential input from the retina, the superior colliculus receives signals from a wide range of other brain regions, providing contextual information, as well as information about the internal state of an animal. All this input is necessary to appropriately adjust an animal’s response to its next exposure to the same danger.
Kühn: “The neuronal circuits underlying our innate behaviors appear to be formed by dedicated and hard-wired pathways. For example, rapidly expanding spots reliably trigger defensive responses in a wide variety of animals including flies, fish, rodents and primates.”
The researchers wanted to explore how the hard-wired circuitry of the superior colliculus is able to support behavioral responses that are flexible. To do so, they focused on a specific group of neurons in the mouse superior colliculus that project to other brain areas.
Specialization and specification
The first thing the team did was explore which neurons connected where. Those experiments revealed a first clear specialization, according to Chen Li, who recently completed her PhD research in the Farrow lab.
“We knew that this particular group of neurons target two other brain regions, but we found that in fact, depending on which target they reach, these neurons form two anatomical and functional separate populations within the superior colliculus.”
While both groups encode similar aspects of the visual scene, they each sample a distinct set of inputs from other brain regions.
“We found that more than 50 brain areas that all provide inputs to the superior colliculus do so with a clear preference for one of these two pathways,” says Li. “While motor-related brain areas tend to innervate neurons of one of the two output pathways, the neurons in the other pathway receive more inputs from brain areas that are associated with cognitive functions.”
Fight or flight? Many brain areas weigh in
The results suggest that information about self-motion has a larger impact on escape reactions, while knowledge about the environment and memories might exert a greater influence on arrest behavior.
Interestingly, both pathways receive similar input from the retina, indicating that the type of visual threat doesn’t favor the activation of one pathway over the other, but that instead, the balance between both downstream pathways is mediated by information about the animal’s activity, internal state, or surroundings.
In an experiment, the researchers were able to shift the balance to freezing and escape behavior of mice by externally inhibiting or stimulating the right pathway.
“Having brain-wide inputs that preferentially affect distinct pathways provides the superior colliculus with a very interesting circuit design,” says Katja Reinhard, a former postdoc in the Farrow lab.
Reinhard co-led the current research project in Leuven and has recently started her own research group at the SISSA research institute in Trieste, where she continues her quest to unravel how our brain integrates information about the environment to adapt behavioral decisions.
“The combination of circuit-specific sampling of inputs and segregated outputs provides hard-wired circuits with the flexibility that is required to respond effectively to imminent threat under different conditions.”
Pathway-specific inputs to the superior colliculus support flexible responses to visual threat. Li, Kühn, et al. Science Advances, 2023. DOI: 10.1126/sciadv.ade3874
Neuro-Electronics Research Flanders (NERF) is a not-for-profit academic research initiative empowered by imec, KU Leuven, and VIB, with the ultimate goal of forming a thorough understanding of brain function at multiple levels of detail ranging from cells and circuits to behavior. New insights into the operation of brain circuits are empowered by the development of novel technologies that integrate neurobiology and nano-scale engineering. NERF develops novel electronic, chemical, and optical tools to monitor and manipulate brain circuits with high spatial and temporal resolution. More info: www.nerf.be.