Fright and flight: Deciding when to escape

June 21, 2018

How does your brain decide what to do in a threatening situation? A new paper published in Nature describes a mechanism by which the brain classifies the level of a threat and decides when to escape.

Escaping from a dangerous situation is crucial for survival, but it is also important to only escape from settings that really are dangerous. This is because decisions to escape are almost always trade-offs between safety and access to things of value. For example, animals need to forage, but when they are scared and hiding in their shelter, they are missing out on vital opportunities of finding food and mates.

This dynamic can be completely debilitating in humans with post-traumatic stress disorder (PTSD) or severe anxiety, as such individuals can become confined to their homes due to pathological fear. Thus it is important for brain circuitry to correctly classify and act on threats in the environment.

Dr. Tiago Branco, Senior Research Fellow at Sainsbury Wellcome Centre, commented: "We are excited to have found a subcellular mechanism for computing the very important decision of running away from threats. This level of detailed understanding not only advances our knowledge of how the brain makes fundamental computations, but also gives us an entry point to figure out what goes wrong in conditions that cause abnormally frequent defensive behaviours, and potentially, how to treat them."

Previous research identified parts of the brain important for escape behaviour, but up until now it wasn't known whether these regions were also involved in evaluating threat level and implementing decisions to escape. A team of neuroscientists led by Dr. Branco working first at the MRC Laboratory of Molecular Biology (LMB) and recently at the Sainsbury Wellcome Centre, systematically tested the innate reactions of mice to looming shadows, as would occur from a bird of prey, an evolutionarily conserved behaviour that is not learnt. Using this approach they have deciphered how escape decisions are implemented in the brain at the algorithmic and mechanistic level, describing the process as a 'threshold computation' of threat level.

The work demonstrated that these decisions are made at the connections between two different parts of the brain: the superior colliculus (SC), which is responsible for integrating information about the threat and estimating the threat level, and the periaqueductal gray (PAG), which represents the activity above the threshold and causes the animal to escape.

The threshold mechanism arises because the SC-PAG connection is very weak and unreliable, so it fails most of the time. It is only when the threat level rises and is sustained that there is sufficient activity to overcome this weak connection and initiate escape. In this way the decision is computed at the level of the synaptic connection between the SC and PAG.

The study makes use of a wide range of techniques, including quantitative behaviour assays that manipulate the probability of whether the animal escapes to threats, and neural activity recordings with head-mounted microscopes and high-density Neuropixels silicon probes. In addition, a special form of chemogenetics was used to specifically inactivate the SC-PAG synapse and thereby prove that the computation of this threshold is implemented by this synaptic connection. Furthermore a computational model was developed that describes the observed behaviour.

The next piece of the puzzle will be to understand how the threshold for the decision is modulated based on past experience and the current conditions of the environment. "Successfully escaping from threats can be a very complicated process that relies on your particular representation of the environment you are in, and what to expect from it. This is at the core of how the brain generates behaviour, and now that we have figured out a critical part of the brain neural circuitry that controls the decision to escape, we can start to explore the computation of complex variables that influence escape decisions, such as how likely it is that safety can be reached, and what are the fastest routes to possible shelters," Dr. Branco concluded.
-end-
This research was supported by a Wellcome Trust/Royal Society Henry Dale Fellowship (098400/Z/12/Z), a Medical Research Council (MRC) grant MC-UP-1201/1, a Wellcome Trust and Gatsby Charitable Foundation SWC Fellowship, MRC PhD Studentship, a Boehringer Ingelheim Fonds PhD fellowship, DFG fellowship, and a Marie Sklodowska-Curie Individual Fellowship and EMBO Long Term Fellowship.

Source:

Read the full paper in Nature: 'A synaptic threshold mechanism for computing escape decisions' By Evans, D.A, Stempel, A.V., et al.

About Sainsbury Wellcome Centre

Sainsbury Wellcome Centre brings together world-leading neuroscientists to generate theories about how neural circuits in the brain give rise to the fundamental processes underpinning behaviour, including perception, memory, expectation, decisions, cognition, volition and action. Funded by the Gatsby Charitable Foundation and Wellcome, Sainsbury Wellcome Centre is located within UCL's School of Life and Medical Sciences and is closely associated with the Faculties of Life Sciences and Brain Sciences. http://www.ucl.ac.uk/swc.

Sainsbury Wellcome Centre

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.