Aarhus Universitets segl

DANDRITE forskningsgruppe afdækker, hvordan vi reagerer på farer og lærer af dem

Nye data har givet ny grundlæggende indsigt i, hvordan hjernen behandler defensiv adfærd som reaktion på både medfødte og tillærte trusler. Disse resultater fremhæver potentialet for præcist målrettede interventioner til at påvirke indviklede hjernekredsløb forbundet med trusselsreaktioner.

The subcortical pathway processes innately-aversive and learned threats. Disruption of the pathway between the lateral thalamus and the lateral amygdala impairs the defensive responses evoked by an innately-aversive looming stimulus and threat learning. However, a noradrenergic receptor blocker reduces the looming stimulus-evoked defensive behaviors and the activity in the amygdala. On the other hand, threat learning remained intact. (Dashed lines represent the disruption of the communication between the lateral thalamus and the amygdala).

Sensing threats is crucial for human survival and safety.
As we grow up, we continue to learn and identify threats and dangers and react accordingly. For example, a child that burns herself by touching a candle will very likely avoid being too close the next time a candle burns. When we hear a fire alarm or smell fire smoke, our brain learns to activate an appropriate defensive response.

Thanks to an intricate connection between two brain regions the thalamus and amygdala – also known as the thalamic-amygdalar circuit – our brain functions as an alarm system, that “goes off” if we feel threatened.

What can we learn from this system? And how can we use this system to treat diseases related to, for example, anxiety and fear?

A hard-wired circuit scaffold

DANDRITE Group Leader Sadegh Nabavi and his lab have studied this specific circuit for many years and its implications for responding to, learning and unlearning threat signals.
In a newly published article in the journal eLife, they demonstrate via systematic circuit interrogation that the subcortical lateral thalamic-amygdalar circuit (shortened LT-BLA pathway) is equally required for threat learning and responding to innate threats, suggesting that the two types of stimuli use the same hard-wired circuit to create a response.

According to Valentina Khalil, a postdoctoral researcher, and the primary author of the study, this has not yet been demonstrated:

“This, to our knowledge, is the first direct evidence documenting that the subcortical thalamic-basolateral amygdala is required for processing an innate visual threat cue.”

What this suggests is that the hardwired circuits which process innate threats may serve as a scaffolding for efficient learning and are thus malleable and prone to external manipulation.

Manipulating the circuit
By comparing the two types of mechanisms, the lab got a detailed insight into the similarities and differences between the circuits processing innate and learned threats and furthermore how they can be manipulated.

Valentina Khalil explains:

“Our findings reveal that by repeatedly exposing individuals to aversive stimuli, we initiated a process of 'unlearning' the threat response. This process led to the extinction of defensive behaviours and was accompanied by a reduction in neural activity associated with perceiving threats."

Moreover, the group demonstrated that the hard-wired circuit is malleable and prone to pharmacological intervention. They achieved this by using a noradrenaline (norepinephrine) receptor blocker, a drug typically employed to treat hypertension and stage fright or social anxiety. This intervention reversibly impaired innate threat processing while leaving threat learning and recall intact.

“It demonstrates that by using an adrenaline receptor blocker, we were able to specifically disrupt innate threat processing in the amygdala without affecting the sensory perception of the threat. This showcases the potential for targeted interventions to modulate complex brain circuits associated with threat response,” Valentina states. 

She emphasizes that while the underlying cellular mechanisms in the circuit still need further investigation, theses findings bring us one step closer to comprehending and addressing til biological underpinnings of fear-like and anxiety-like behaviours.