Summary: Mice can readily learn to suppress their innate behavioral response to escape, effectively ignoring stimuli they determine to pose no threat.
Source: Sainsbury Wellcome Center
Some behaviors that are crucial to survival appear to be hard-wired, meaning that they occur without previous experience. For example, many prey organisms naturally know how to escape to safety from perceived threats. However, it is also important for an organism to learn about the world and adapt to its ever-changing circumstances. How does the nervous system enact such flexible decisions over a lifetime?
Neuroscientists at the Sainsbury Wellcome Centre at UCL studied the flexibility of escape behavior in mice.
In a new study, published today in Current Biology, the researchers show that, while escape behavior can be robustly elicited in a laboratory setting, mice can nonetheless readily learn to suppress their escape response, effectively ignoring stimuli that are determined to pose no threat.
“An obvious example is the domestication of cattle and pets. This clearly shows that organisms learn that things they initially interpreted as threatening may not be so. Cattle for example, were once fearful of human beings but at some point they learned that humans could become a reliable source for food, shelter and even protection from other species,” said Troy Margrie, Group Leader at the Sainsbury Wellcome Centre and corresponding author on the paper.
To explore this behavioral flexibility, researchers in the Margrie lab firstly presented mice with an overhead expanding dark disk, called a looming stimulus, to simulate a predator moving towards them from above.
They found they could evoke highly robust escape by isolating mice for a couple of days before testing and used this robust model of escape as a starting point for quantifying its flexibility. Then, as an initial approach, they presented this looming stimulus repeatedly to observe whether the mice would eventually stop responding to it.
However, after many presentations of the stimulus, mice did not consistently learn to suppress their escape behavior.
“Funnily enough, one of the problems we faced is that under the right conditions mice react so robustly to high contrast looming stimuli, which means they run away and hide, and it can therefore take a very long time to expose mice to enough stimuli for them to reliably suppress their escape response,” said Steve Lenzi, Research Fellow in the Margrie lab at SWC and first author on the paper.
And so the researchers introduced a physical barrier preventing access to the nearby shelter and adjusted the contrast of the looming stimuli, to make a gradient from low threatening to high threatening. These adjustments led to a consistent suppression of the escape response in mice. The neuroscientists showed that this suppression was robust and it persisted for several weeks.
Furthermore, the suppression was specific to the stimulus, meaning that the mice continued to escape when presented with a different threatening stimulus, such as a loud noise instead of the looming stimulus.
They also showed that the degree of suppression of escape was very much dependent on recent threat-escape history.
“This suggests that escape is not simply reflexive but dependent on threat memory and is therefore under cognitive control,” said Troy Margrie.
“Although this work focuses fundamentally on behavior, we believe that the paradigm we have established here can be used to probe the neural circuitry underpinning the flexibility of innate behaviors so we also apply this in the search for, and study of, brain regions that are involved in the regulation of escape behavior and we hope others will do the same,” said Steve Lenzi.
In addition to exploring how threat history affects the control of escape behavior, the researchers looked at the impact of social environment. In the study, the team compared the escape behavior of mice that were group-housed versus individually-housed.
They found that mice that lived collectively in large groups, of 20 individuals, were much less likely to escape when tested individually. Whereas mice that were isolated and lived on their own for a while, appeared to be much more vigilant or perhaps reactive.
“Initially we wanted to understand whether generic experience influences the decision to escape. Single housing or group housing is a very easy and natural way to introduce experiential differences in laboratory mice.
“Plus, there are many examples from field studies that show that group statistics can profoundly influence predator avoidance or surveillance behaviors. Animals that are alone need to be more vigilant, whereas in a flock they can spread the surveillance among the group,” said Steve Lenzi.
There are many open questions that follow-on from these findings and the next steps for the researchers are to dig into the mechanisms of how this kind of learning occurs.
The Margrie lab plan to use this ethologically-relevant protocol to begin to understand the neural mechanisms of how animals learn to suppress escape and specifically, how different systems in the brain interact with the escape circuitry to enable this flexibility of behavior.
Understanding this niche will begin to help tackle the wider unknown question of how learning interacts with our innate tendencies to engage in certain behaviors.
Funding: This research was funded by the Sainsbury Wellcome Centre Core Grant from the Gatsby Charitable Foundation (GAT3755) and Wellcome (219627/Z/19/Z).
Threat history controls flexible escape behaviour in mice
Individually housed, but not group-housed, mice show robust escape to looming stimuli
Mice can learn to suppress escape, and LSE memory is long lasting
LSE is not a general adaptation since it is stimulus specific
LSE is not simply habituation and is dependent on recent threat-escape experience
In many instances, external sensory-evoked neuronal activity is used by the brain to select the most appropriate behavioral response.
Predator-avoidance behaviors such as freezing and escape are of particular interest since these stimulus-evoked responses are behavioral manifestations of a decision-making process that is fundamental to survival.
Over the lifespan of an individual, however, the threat value of agents in the environment is believed to undergo constant revision, and in some cases, repeated avoidance of certain stimuli may no longer be an optimal behavioral strategy.
To begin to study this type of adaptive control of decision-making, we devised an experimental paradigm to probe the properties of threat escape in the laboratory mouse Mus musculus.
First, we found that while robust escape to visual looming stimuli can be observed after 2 days of social isolation, mice can also rapidly learn that such stimuli are non-threatening. This learned suppression of escape (LSE) is extremely robust and can persist for weeks and is not a generalized adaptation, since flight responses to novel live prey and auditory threat stimuli in the same environmental context were maintained.
We also show that LSE cannot be explained by trial number or a simple form of stimulus desensitization since it is dependent on threat-escape history.
We propose that the action selection process mediating escape behavior is constantly updated by recent threat history and that LSE can be used as a robust model system to understand the neurophysiological mechanisms underlying experience-dependent decision-making.