Overview: Mice can easily learn to suppress their innate behavioral response to escape, effectively ignoring stimuli that they determine do not pose a threat.
Source: Sainsbury Wellcome Center
Some behaviors critical to survival seem to be stuck, meaning they take place with no previous experience. For example, many prey organisms naturally know how to get to safety from perceived threats. However, it is also important for an organism to get to know the world and to adapt to the ever-changing conditions. How does the nervous system absorb such flexible decisions throughout a lifetime?
Neuroscientists at the Sainsbury Wellcome Center at UCL studied the flexibility of escape behavior in mice.
In a new study, published today in current biologythe researchers show that while escape behavior can be powerfully elicited in a laboratory setting, mice can nevertheless easily learn to suppress their escape response, effectively ignoring stimuli determined to pose no threat.
“An obvious example is the domestication of livestock and pets. This clearly shows that organisms are learning that things that they initially interpreted as threatening may not be so. For example, cattle were once afraid of humans, but at some point they learned that humans could become a reliable source of food, shelter and even protection from other species,” said Troy Margrie, group leader at the Sainsbury Wellcome Center and corresponding author on the paper. .
To investigate this behavioral flexibility, researchers in the Margrie lab first presented mice with an aboveground expanding dark disk called a menacing stimulus to simulate a predator moving toward them from above.
They found that they could elicit a very robust escape by isolating mice for a few days before testing and used this robust escape model as a starting point for quantifying its flexibility. Then, as a first approach, they repeatedly presented this threatening stimulus to see if 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 was that under the right conditions, mice react so vigorously to high-contrast threatening stimuli, meaning they run away and hide, and therefore can take a very long time to expose mice.” sufficient stimuli to reliably suppress their escape response,” said Steve Lenzi, Research Fellow in SWC’s Margrie lab and lead author of the paper.
And so the researchers introduced a physical barrier that prevented access to the nearby shelter and adjusted the contrast of the threatening stimuli, to create a gradient from low threatening to high threatening. These adaptations led to consistent suppression of the escape response in mice. The neuroscientists showed that this suppression was robust and lasted for several weeks.
In addition, the suppression was stimulus specific, meaning that the mice continued to escape when given another threatening stimulus, such as a loud noise instead of the threatening stimulus.
They also showed that the degree of escape suppression was highly dependent on recent threat escape history.
“This suggests that escape is not only reflexive, but relies on threat memory and is therefore under cognitive control,” said Troy Margrie.
“While this work focuses fundamentally on behavior, we believe that the paradigm we established here can be used to investigate the neural circuits that underpin the flexibility of innate behavior, so we also apply this to our search for and study.” brain regions involved in regulating escape behavior and we hope others will do the same,” said Steve Lenzi.
In addition to examining how threat history affects control over escape behavior, the researchers looked at the impact of the social environment. In the study, the team compared the escape behavior of mice housed in a group versus housed individually.
They found that mice living together in large groups of 20 individuals were much less likely to escape when tested individually. While mice that were isolated and lived on their own for a while were found to be much more vigilant or perhaps more reactive.
“Initially, we wanted to understand whether generic experience influences the decision to escape. Single person housing or group housing is a very easy and natural way to introduce experience differences in laboratory mice.
“In addition, there are many examples from field studies showing that group stats can have a profound impact on predator avoidance or guarding behavior. Animals alone need to be more vigilant, while in a herd they can spread guard among the group,” said Steve Lenzi.
There are many open questions following these findings, and the next steps for the researchers are to dig into the mechanisms of how this type of learning occurs.
The Margrie lab plans to use this ethologically relevant protocol to understand the neural mechanisms of how animals learn to suppress escape and, in particular, how different systems in the brain interact with the escape circuit to enable this flexibility of behavior. .
Understanding this niche will help address the broader unknown question of how learning interacts with our innate tendencies to engage in certain behaviors.
Financing: This research was funded by the Sainsbury Wellcome Center Core Grant from the Gatsby Charitable Foundation (GAT3755) and Wellcome (219627/Z/19/Z).
About this news about behavioral neuroscience research
Original research: Open access.
†Threat history controls flexible escape behavior in miceby Troy Margrie et al. current biology
Threat history controls flexible escape behavior in mice
- Housed individually, but not in group housing, mice demonstrate robust escape from threatening stimuli
- Mice can learn to suppress escape, and LSE memory lasts a long time
- LSE is not a generalized adaptation because it is stimulus specific
- LSE is not just habituation and relies on recent threat escape experience
In many cases, external sensory-evoked neuronal activity is used by the brain to select the most appropriate behavioral response.
Predator avoidance behaviors such as freeze and escape are of particular interest, as these stimulus-evoked responses are behavioral manifestations of a decision-making process fundamental to survival.
However, throughout an individual’s lifetime, the threat value of agents in the environment is believed to be constantly revised, and in some cases, repeated avoidance of certain stimuli is no longer an optimal behavioral strategy.
To study this type of adaptive control of decision-making, we developed an experimental paradigm to investigate the properties of threat escape in the laboratory mouse. Mus musculus†
First, we found that while a robust escape to visually threatening stimuli can be observed after 2 days of social isolation, mice can also quickly learn that such stimuli are nonthreatening. This learned suppression of escape (LSE) is extremely robust and can persist for weeks and is not a common adaptation as flight responses to new live prey and auditory threat stimuli were maintained in the same environmental context.
We also show that LSE cannot be explained by the trial number or a simple form of stimulus desensitization, as it depends on the escape history of the threat.
We propose that the action selection process that mediates escape behavior is continuously 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.
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