Neuroscience Study Sheds Light on Fear Response

The amygdala is a part of the brain that processes emotions such as anger and fear. The amygdala is also where emotional memories are formed and threatening stimuli are sorted from non-threatening ones.

In a recent study, published in the journal Neuron, researchers show that it’s the prefrontal cortex that activates inhibition cells in the amygdala to control fearful responses to non-threatening stimuli. They say the findings may help to treat anxiety disorders. 

“It’s this communication between the prefrontal cortex and inhibitory cells in the amygdala that ends up desynchronizing the amygdala such that it’s not really able to drive all of the other downstream effectors of fear,” said lead study author Professor Ekaterina Likhtik, (GC/Hunter, Biology, Neuroscience), co-chair of the CUNY Neuroscience Collaborative. 

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These are a specialized group of inhibitory nerve cells, known as somatostatin-expressing interneurons, linked to a number of psychiatric disorders including depression, Likhtik said.

In experiments for the study, researchers were able to demonstrate that mice froze less often in response to non-threatening sound cues when prefrontal cortex terminals in the basolateral amygdala were stimulated.

Likhtik points to the freezing response as an example of a fearful, defensive behavior triggered by the amygdala. “We know that the amygdala activates the freezing response,” she said. “What's interesting about the defensive freezing response is that it's something that you see across species of mammals.”

“The reason we're interested in this is because in a lot of psychiatric disorders that engage emotion regulation — for example, post-traumatic stress disorder [PTSD] and other anxiety disorders — this kind of discrimination of threat versus non-threat is compromised.” 

This can often be seen as “generalized fear” — when someone responds in a generalized, fearful way to non-threatening stimuli such as loud noises.

“Overgeneralized fear is one of the cardinal symptoms in anxiety and stress-induced disorders,” Likhtik said. “It’s characterized by indiscriminate defensive or avoidant behaviors to threatening and to non-threatening situations. This kind of vigilance takes a toll on the body by driving the autonomic nervous system, disrupting sleep, and makes life more difficult overall.”

So, one important goal for treating anxiety disorders is to tamp down fearful reactions to non-threats, Likhtik said, “allowing people to engage with the world more fully.”

But the exact neural mechanisms the prefrontal cortex engages in the amygdala when learning to distinguish threats remain unclear, she said.

“So, this really helps us to gain a footing to understand more specific neural mechanisms downstream of the prefrontal cortex, how prefrontal activity modulates circuit function in the amygdala to tamp down these fear responses to non-threatening stimuli,” the professor said. 

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