Neural Circuitry of Fear and Anxiety

 

Towards the extinction of Anxiety, Phobias and Psychological Traumas

 

Two very important studies on fear were recently published in the same issue of the scientific journal Nature, referring to a short-term and long-term fear retrieval circuit.

 

Let us consider  a fire alarm as a case study so that we can relate to the experimental setting of the studies.

 

"We only hear the fire alarm in our building during fire drills. I heard the alarm this morning and then we were told to evacuate because there was a fire on the floor."

 

 

What happens if you hear the alarm again 6 hours later? You are frightened because you think it is the real thing. You recall the experience you had 6 hours ago. What happens for this short-term repetition of the stimulus?

 

 

What happens if you hear the alarm a few days later? You are frightened for the same reason. What happens for this long-term repetition of the stimulus?

 

 

Why is it important to know the mechanism behind this? Because then you could extinguish fear manifestations, such as anxiety, phobias and psychological traumas.

 

 

 

 

A “PREFRONTAL CORTEX- AMYGDALA” CIRCUIT FOR SHORT-TERM FEAR RETRIEVAL
A “THALAMUS – AMYGDALA” CIRCUIT FOR FEAR MANIFESTATION AND LONG-TERM RETRIEVAL 


http://www.nature.com/nature/journal/v519/n7544/full/nature14030.html  View the editor’s summary on the right
 
http://www.nature.com/nature/journal/v519/n7544/full/nature13978.html View the editor’s summary on the right

Comment on the above two studies: http://www.nature.com/nrn/journal/v16/n3/full/nrn3932.html

 

 

Here is how media/social media presented the two studies:

 

 

 

SCHEMATICAL REPRESENTATION OF THE TWO CIRCUITS

 

 

https://www.sciencenews.org/article/newly-identified-brain-circuit-hints-how-fear-memories-are-made
Science News | Ashley Yeager
Newly identified brain circuit hints at how fear memories are made

 

 

 

http://loonylabs.org/2015/01/19/anxiety-ptsd/
LOONYLABS
After rats were conditioned to fear a tone associated with a mild shock, their overt behavior remained unchanged over time, but the pathway engaged in remembering the traumatic event took a detour, perhaps increasing its staying power.

“While our memories feel constant across time, the neural pathways supporting them actually change with time,” explained Gregory Quirk, Ph.D.
“Uncovering new pathways for old memories could change scientists’ view of post-traumatic stress disorder, in which fearful events occur months or years prior to the onset of symptoms.”

Immediately after fear conditioning, a circuit running from the prefrontal cortex, the executive hub, to part of the amygdala, the fear hub, was engaged to retrieve the memory. But several days later, the group discovered that retrieval had migrated to a different circuit – from the prefrontal cortex to an area in the thalamus, called the paraventricular region (PVT). The PVT, in turn, communicates with a different central part of the amygdala that orchestrates fear learning and expression.

The researchers spotted the moving memory using a genetic/laser technique called optogenetics, which can activate or silence specific pathways to tease apart their workings.

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Personal Comments

 

Name a biochemical reaction that generates the emotion of fear: Binging of BDNF (e.g. from the paraventricular thalamus) to the amygdala.

Thalamus (“Chamber” or “Room” in Greek) is a Brain Control Room or Brain Switchboard accepting input from sensors.
Wikipedia: “Every sensory system (with the exception of the olfactory system) includes a thalamic nucleus that receives sensory signals and sends them to the associated primary cortical area.”

 

 

http://loonylabs.org/2015/01/19/anxiety-ptsd/
LOONYLABS
“Simply infusing BDNF into the central amygdala area caused mice to freeze in fear, suggesting that it not only enables the formation of fear memories, but also the expression of fear responses.”

 

 

http://www.cshl.edu/1282-a-new-brain-circuit-that-controls-fear-is-identified.html

 

 

Cold Spring Harbor Laboratory | News and Features | Jaclyn Jansen, Science Writer

 

 

Cold Spring Harbor, NY – Some people have no fear, like that 17-year-old kid who drives like a maniac. But for the nearly 40 million adults who suffer from anxiety disorders, an overabundance of fear rules their lives. Debilitating anxiety prevents them from participating in life’s most mundane moments, from driving a car to riding in an elevator. Today, a team of researchers at Cold Spring Harbor Laboratory (CSHL) describes a new pathway that controls fear memories and behavior in the mouse brain, offering mechanistic insight into how anxiety disorders may arise.

 

 

 

https://bbrfoundation.org/brain-matters-discoveries/scientists-pick-apart-a-fear-circuit-in-the-brain-and-find-a-molecular

 

 

Brain and Behavior Research Foundation | Discoveries |Bo Li Ph.D.

 

 

“The key orchestrator is a section of the thalamus, a central relay station that stands between incoming sensory information and the brain’s cerebral cortex – its incredibly sophisticated information processor.”

 

 

A part of the thalamus called the PVT (paraventricular nucleus), already known to be sensitive to stress, acts as a sensor for tension – both physical and psychological. In their new research, Dr. Li’s team showed, in his words, that “the PVT is specifically activated when animals learn to fear, or when they recall fear memories.”  The team saw that neurons in the PVT extend tendrils deep into the central amygdala. And when the scientists experimentally interfered with those connecting links, animals were not able to learn to fear.

 

 

This fact suggests the PVT-amygdala connection would make a promising target for drugs to suppress the formation of fear memories. The question is: what exactly to target?  A potentially important clue discovered by Dr. Li’s team is a protein called BDNF.

 

 

 

http://www.sbindependent.org/researchers-identify-fear-circuit-in-the-brain/

 

 

Stony Brook Independent | By Colleen Mertes

 

 

Co-author Jason Tucciarone said in an article published by the Stony Brook Newsroom that the greater understanding of how fear functions in the brain could “provide clues to faulty processing of threats that can lead to anxiety, phobias, and, perhaps, post traumatic stress disorder.”

 

 

The team first explored the thalamus, the “switchboard” of the brain (…)

 

 

 

ERIC KANDEL, ONE OF THE MOST FAMOUS NEUROSCIENTISTS and NOBEL PRIZE WINNERS, ON TV

 

One of the most popular American TV shows, the C. Rose Show, created a series called “The Brain Series” with episodes that are presented regularly among shows with interviews of different personalities.  

 

From Wikipedia: In 2010 Rose and cohost Eric Kandel began "The Brain Series", episodes featuring neuroscientists and other experts;[3] the series was later released on DVD.[4]

 

 

3rd Series – Episode 2 - Aggression

 

David Anderson of the California Institute of Technology, Richard Tremblay of University of Montreal, Johanna Ray Vollhardt of Clark University, Emil Coccaro of University of Chicago, Adrian Raine of University of Pennsylvania, and Eric Kandel.

 

Air Date: March/5/2015

 

E. Kandel introduces the fundamental glossary, the brain regions that will be mentioned during the talk.

 

 

 

[Time from start: 7.00] C. Rose invites D. Anderson to speak on the “Biology of Aggression”

 

Where is aggression in the brain?

 

Which other manifestation or behavioral function is linked to aggression?

 

Mating.

 

A fundamental observation. Mating and Aggression; mutually exclusive behaviors or reinforcing cues.

  • At periods where animals mate there is also increased animal aggression.
  • Males direct mating towards females and fighting towards other males.

 

They tried to find the cells for aggression. They looked in an ancient, evolutionary conserved region of the brain, the hypothalamus. In this area they found cells that are electrically activated by mating or fighting. Some are activated by mating, some by fighting and some, about 25% of the total population, by both mating and fighting.

 

 

They found an experimental system that allowed the control of the activation of these cells by optogenetics, that is by exposure of the mouse to light.

 

 

In the second video shown, in a cage where a male mouse is resident, another male mouse is introduced. The latter will be perceived as an intruder and will be attacked. Upon switching off of the cells responsible for aggression, the attack stops.