A new study published in Molecular Psychiatry shed light on a discovery related to a process called adaptive defensive learninga mechanism that allows us not to live constantly on alert. When the brain perceives a dangerreacts in a few moments: he can immobilize (the classic freezing), escape or attack. These automatic responses are essential for survival. But what happens if the danger never materializes? What if, for example, a menacing shadow appears multiple times without ever transforming into a real predator? In these cases, continuing to react as if the threat were real would be one waste of energy and resources. The brain must learn to distinguish “real danger” from only apparent danger, adapting its responses. The new study sheds light on the “director” of this process: a tiny area of the brain called interpeduncular nucleus (IPN)located in the midbrain, a deep and ancient region of the brain. This structure, so far little known, plays a central role in modulating the fear and in deciding when to stop having them.
The brain’s strategies when faced with fear
The defensive responses they are not all the same: they depend on theintensity and from predictability of the threat. When a danger appears sudden and uncontrollable, instinctive reactions such as escape or immobilization prevail. If, however, the brain recognizes that the threat is predictable and not actually harmful, circuits come into play that promote calm and curiosity. THE’IPN is at the center of this equilibrium: if its activity remains high, it maintains it state of alert and blocks exploration; if it decreases, it allows the brain to move from fear to evaluationpromoting adaptation. In this way, the organism not only defends itself, but also learns to manage emotions related to fear, developing a form of resilience.
Training the brain not to hide from danger: the new study on mice
To understand how this adaptation occurs, the researchers conducted an experiment on micesimulating a dangerous situation. An expanding dark shadow was cast from above, one looming visual stimulus which imitates the approach of a predator. At the first exposurethe mice reacted becoming immobilized or looking for shelter. However, after three days consecutive experiments, their behavior changed: they remained hidden for less time and dedicated more time toexploration. It was proof of a adaptive learning: the brain had “understood” that that threat did not represent a real danger.
By analyzing the activity ofIPN (already known for its involvement in anxiety and stress processes) via fiber photometrya technique that allows us to observe neuronal activity in real time, the researchers discovered that a specific population of neurons was activated in the first exposures to the predator’s shadow. As the days went by, however, their activity decreased in parallel with the reduction of fearful behaviors. When these neurons came artificially inhibitedthe mice almost completely stopped hiding; keeping them active instead prevented them from learning that the threat was harmless. The IPN therefore behaves like a fear regulatorcapable of amplifying or attenuating the defensive response and guiding the brain towards adaptation
Two circuits, two functions
Scientists then discovered that IPN does not act alone, but through two distinct circuitseach with a specific task. A part of the neurons of the IPN communicates with the laterodorsal tegmental nucleus (LDTg)another brain region that sends excitatory signals to brain areas implicated in curiosity, motivation, and exploration. The IPN–LDTg connection uses the GABA as a neurotransmitter and is therefore inhibitory: by reducing the activity of the LDTg, the IPN temporarily “puts to sleep” exploratory behaviors when the threat appears relevant.
Another population of neurons in the IPN, those that express somatostatin (Sst)instead seems responsible for avoidance behaviors. These neurons, unlike the previous ones, they don’t fit: They continue to activate even when the threat is no longer dangerous. When researchers have them “turned off”, the mice showed less fear and more explorationeven in new situations. This suggests that Sst neurons may contribute togeneralized anxietythat feeling of constant danger that persists even in the absence of real threats.
