The Brain on Fear

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The Brain on Fear

Scientists uncover the neurons in the mouse brain responsible for linking the sight of a looming object to scared behavior.

By Ruth Williams | June 25, 2015

WIKIMEDIA, RAMAAnimals respond to fear in predictable ways. A mouse confronted with danger is likely to either freeze in place or run for its life. But how this primal response is elicited in the brain has remained murky. A study in mice published in Science today (June 25) reveals specific neuronal wiring that runs between the eye and the amygdala—the emotion and decision-making center of the brain—that translates the sight of an advancing threat to the animal’s instinct to freeze or flee.

“One of the big challenges in neuroscience is to understand the relationship between molecules, cells, [and] synapses on one hand, and microcircuit function and behavior on the other,” said neuroscientistPeter Jonas of the Institute of Science and Technology in Klosterneuburg, Austria, who was not involved in the work. “It is nice to bridge these different levels and . . . this paper provides a nice example of how this is becoming possible.”

Fear behavior is critical for survival, and animals and humans use all their sensory inputs to detect, assess, and escape from life-threatening situations. In the case of visual threats, researchers have identified cells in the retina that respond to looming objects. Then, in the midbrain, a structure called the superior colliculus, which receives retinal neuron inputs, contributes to avoidance and defensive behavior. “However, the neuronal cells mediating these behaviors, and the circuits linking them to fear response remain unknown,” wrote Peng Cao of the Chinese Academy of Sciences in Beijing in an e-mail to The Scientist.

As a first step, Cao and his colleagues optogenetically stimulated all neurons in the superior colliculus of mice and found that this was sufficient to produce a fear response in the animals—the mice froze in place. The researchers then engineered specific subtypes of superior colliculus neurons to respond to light and found that stimulation of neurons expressing the calcium-binding protein parvalbumin (PV) produced a similar fear response—the mouse first attempted to escape but quickly froze. Stimulation of neurons expressing somatostatin (SST) or vasoactive intestinal peptide (VIP)—both peptide hormones—elicited no fear response at all.

To determine whether the PV neurons were indeed responsible for transmitting information about visual threats, the researchers displayed a virtual soccer ball that appeared to roll toward a stationary animal. Recordings taken from the animal’s superior colliculus revealed that the virtual ball induced high activity in the PV neurons.

The team went on to show that the PV neurons projected to a number of different regions within the brain, including a structure called the parabigeminal nucleus (PBGN), which leads to the amygdala. Local optogenetic stimulation of the PBGN induced the same fear response as that seen during PV neuron stimulation in the superior colliculus.

“To me that was a surprise—that [the neural signals] take so many stages to arrive at the fear place [the amygdala],” said Botond Roska of the Friedrich Meischer Institute for Biomedical Research in Basel, Switzerland, who also was not involved in the study. “I thought that this pathway would be a more direct and specific connection because it must be [processed] very fast.” Indeed, a quick decision is essential when facing a dangerous predator or falling boulder.

Roska suggested that each stage of the pathway might hone the signal somewhat, such that the animal “is absolutely sure [what they’ve seen] is truly a threat.”

In addition to working out how the separate stages might modify the transmission, Cao would like to know whether humans share the same pathway as rodents and, if so, whether the pathway plays a role in any mental disorders.

“Activation of the PV neurons made the mice form fear memories and conditioned place-aversion,” he wrote. “Repeated activations of these neurons caused depression-like behaviors.” Both of these are similar to the symptoms seen in post-traumatic stress disorder, Cao noted. “Obviously, we need more experiments to support this idea.”

C. Shang et al., “A parvalbumin-positive excitatory visual pathway to trigger fear responses in mice,” Science, 348:1472-1477, 2015.

reported from here

Where and how are fear-related behaviours and anxiety disorders controlled?

21.11.2013 - PRESS RELEASE

Neurosciences, cognitives sciences, neurology and psychiatry

A team of researchers at Inserm led by Cyril Herry (Inserm Unit 862, “Neurocentre Magendie,” Bordeaux) has just shown that interneurons located in the forebrain at the level of the prefrontal cortex are heavily involved in the control of fear responses. Using an approach combining in vivo recordings and optogenetic manipulations in mice, the researchers succeeded in showing that the inhibition of parvalbumin-expressing prefrontal interneurons triggers a chain reaction resulting in fear behaviour. Conversely, activation of these parvalbumin interneurons significantly reduces fear responses in rodents. 

This research is published in the journal Nature

Some traumatic events may lead to the development of severe medical conditions such as anxiety disorders or posttraumatic stress disorder (PTSD).

Anxiety disorders have a prevalence of approximately 18% worldwide.

Despite successful treatments, some patients relapse, and the original symptoms reappear over time (fear of crowds, recurring nightmares, etc.). An understanding of the neuronal structures and mechanisms involved in this spontaneous recovery of traumatic responses is essential.

All observations made by researchers indicate that fear behaviours are controlled in the forebrain at the level of the dorsomedial prefrontal cortex. This control of fear behaviour is based on the activation of neurons in the prefrontal cortex that are in contact with specific areas of the amygdala.

Using an innovative approach combining electrophysiological recording techniques, optogenetic manipulations and behavioural approaches, the researchers were able to demonstrate that fear expression is related to the inhibition of highly specific interneurons—the parvalbumin-expressing prefrontal interneurons.

More specifically, inhibition of their activity disinhibits the activity of the prefrontal projection neurons, and synchronises their action.

Synchronisation of the activity of different neuronal networks in the brain is a fundamental process in the transmission of detailed information and the triggering of appropriate behavioural responses. Although this synchronisation had been demonstrated as crucial to sensory, motor and cognitive processes, it had not yet been examined in relation to the circuits involved in controlling emotional behaviour.

“Our results identify two complementary neuronal mechanisms mediated by these specific interneurons, which accurately coordinate and increase the neuronal activity of prefrontal projection neurons, leading to fear expression,” explains Cyril Herry. 

The identification and better understanding of these neuronal circuits controlling fear behaviour should allow the development of new treatment strategies for conditions such as posttraumatic stress disorder and anxiety disorders. “We could, for example, imagine the development of individual markers for these specific neurons, or the use of transmagnetic stimulation approaches to act directly on excitatory or inhibitory cells and reverse the phenomena.”

How is fear analysed in an animal?

From an experimental standpoint, the classic Pavlovian conditioning procedure involves associating one stimulus, such as a sound, with another, unpleasant stimulus, such as a small electric shock. This first step allows the animal to establish a persistent aversive memory. In other words, the animal comes to remember and learn that the sound is associated with an unpleasant state, and an immobility response is routinely triggered, which is a good indication of fear in an animal.

In the second step, the extinction procedure involves repeated presentation of the sound alone, inducing a temporary inhibition of the conditioned fear responses. This inhibition is only temporary, as the mere passage of time favours the spontaneous recovery of the conditioned fear responses, which, from the clinical standpoint, may be associated with the phenomenon of relapse into traumatic responses seen following the treatment of posttraumatic stress disorder using exposure-based therapies.

TO CITE THIS PAGE :
Press release – Inserm press room – Where and how are fear-related behaviours and anxiety disorders controlled?

Link :
http://presse-inserm.fr/en/where-and-how-are-fear-related-behaviours-and-anxiety-disorders-controlled/10232/