How the brain remembers to fear danger

(Credit: iStockphoto)

It’s been long known that human survival depends a bit on something called “fight or flight.” How this alarm in our brain first goes off, and what other parts of the brain are mobilized to express fear—and remember to avoid danger in the future—have been less clear.

In a new study with mice, researchers identify a new life-preserving circuit that is responsible for recognizing and remembering threats, as well as activating the brain to respond to danger.

“This research enriches our understanding of brain anatomy and normal functioning in fear memory,” says coauthor Jason Tucciarone, a PhD student in the Medical Scientist Training Program (MSTP) and the neurobiology and behavior department at Stony Brook University.

“It also may provide clues to faulty processing of threats that can lead to anxiety, phobias, and, perhaps, post-traumatic stress disorder.”

Researchers first looked at the thalamus, the part of the brain known as the “switchboard.”  In particular, they focused on the paraventricular nucleus of the thalamus (PVT), “an area that is readily activated by both physical and psychological stressors,” they write in the paper that appears in Nature.

Sensitive to threats

As part of the experiment, the researchers used mild foot shocks to simulate danger—and also genetically altered mice to study the role specific parts of the circuit play in protecting the mice from “danger.”

First, they confirmed that the PVT was indeed highly sensitive to threats. They then looked at the neurons in the posterior PVT (pPVT) that were communicating with the lateral division of the central amygdala (CeL), where neuroscientists say is a site of fear memories.


Through a series of experiments that suppressed communications coming from these neurons, they found that the pPVT plays an important role in conditioning the mice to fear certain situations and to remember those fears. They also demonstrated that this knowledge was “hard wired” into the neuronal synapses.

But what chemical messenger do the pPVT neurons send off to deliver this information to their cousins in the CeL? The researchers hypothesized that the messenger might be brain-derived neurotrophic factor (BDNF), a protein known to regulate synaptic functions.

To test this hypothesis, the researchers created mice without the gene to produce BDNF or without a BDNF receptor. Both kinds of mice exhibited an impaired ability to recognize danger, even after being conditioned to do so. The researchers also tested the effect of BDNF on mice that had not been genetically altered by infusing their brains with BDNF, causing a “robust” response to danger.

The communications transmitted by BDNF produced in pPVT neurons and picked up by CeL receptors, the researchers conclude, “facilitates not only the formation of stable fear memories but also the expression of fear responses.”

The National Institutes of Health, the Dana Foundation, the National Alliance for Research in Schizophrenia and Affective Disorders, the Louis Feil Trust, the Stanley Family Foundation, and a Harvey L. Karp 27 Discovery Award supported the research.

Source: Stony Brook University