Adolescence is a Sensitive Period for Fear Learning

October 23, 2015 · Posted in Neurobiology · Comment 


Adolescence can be a time of vulnerability to illness. Anxiety disorders increase during this period, and three-quarters of adults with anxiety disorders trace the illness back to their childhood or adolescence. The most common treatments for anxiety disorder are based on the idea of fear extinction. A certain stimulus, like a social situation or seeing a spider, provokes a fear reaction in the brain. Through gradually increasing exposure to the stimulus and extinction training, the person becomes desensitized to the stimulus. New research on rodents presented by Francis S. Lee at the 2015 meeting of the Society for Biological Psychiatry suggests that the extinction process is diminished during adolescence.

At specific stages of maturation, neural circuits related to particular abilities can become flexible. Brain and behavior become sensitive to and are increasingly shaped by experience. Studies of rodents and humans have shown that adolescence is a time when the neural circuitry for fear extinction is in flux. In mice, this period falls around their 29th day of life. Lee reported that around this time, the mice begin to exhibit resistance to extinction of fear learning.

In adolescent rodents, there is a surge of contextual fear learning and retrieval that is mediated by hyper-connectivity of the ventral hippocampus and the amygdala to the prelimbic part of the prefrontal cortex. In contrast, the pathway from the amygdala to the infralimbic cortex mediates the extinction of this type of learning. Because the prelimbic pathway for fear learning is overactive, the infralimbic pathway for extinction learning is less effective.

Adolescent mice temporarily lose their ability to retrieve memories related to cue-dependent (as opposed to context-dependent) fear learning. Remarkably, when these animals proceed into adulthood, the fear learning associated with cues returns and becomes accessible again.

This could help explain how teenagers can lose fear conditioning to cues (for example, speeding through a red light) they learned in childhood. The fear is forgotten (or becomes inaccessible) in adolescence, but then what had been learned is again “remembered” (retrieved) in adulthood. Read more

Exposure to Stress Hormone Leads to Poor Decision-Making

April 8, 2015 · Posted in Risk Factors · Comment 

stress hormone

Adolescence may be a period of particular vulnerability to the effects of stress. New research by Shannon Gourley indicates a possible mechanism for this vulnerability. When Gourley exposed adolescent mice to low levels of the stress hormone corticosterone (the equivalent to human cortisol), they developed habit-based rather than goal-oriented decision-making, leading to behaviors that resembled human depression, which lasted into adulthood. Adult mice that were exposed to the low levels of corticosterone were not affected by it.

Gourley also used an alternative method of producing these stress responses a second time by silencing the trkB receptor for brain-derived neurotrophic factor (BDNF) in the amygdala and hippocampus of the mice. The depression-like behaviors that resulted, such as lack of motivation, were able to be reversed by treating the mice with 7,8-dihydroxyflavone, a drug that activated the trkB receptor. In the adolescent mice, this treatment had antidepressant effects that lasted into adulthood, even though the treatment stopped earlier.

An Animal Model of Poor Judgment in Adolescence: Previous Learning Suppressed

March 1, 2013 · Posted in Neurobiology · Comment 


As young mice transition into adolescence, they experience a “sensitive” period in which their context-based fear memories are temporarily suppressed. In a recent study, young animals learned to avoid an environment associated with a mild shock. Later, when they entered adolescence, this learning was temporarily forgotten or suppressed. However, when the same mice aged into adulthood, they reacquired this learned fear memory and began to again avoid the environment associated with the earlier shock. This temporary loss of fear memory differs in mice depending on their genes.

At the 2012 meeting of the Society of Biological Psychiatry, researcher Francis S. Lee reported that mice with a certain genetic variation display an impairment of this fear memory process. There are several common variants of the gene responsible for the production of brain-derived neurotrophic factor (BDNF), which protects neurons and is necessary for long-term memory. Mice with the poorer functioning variant known as Val66Met (as opposed to the better functioning Val66Val) fail to recall the earlier fear-related events not only in adolescence, but also in adulthood when the fear memory is usually retrievable again.

Editor’s Note: In mice and humans, Val66Val is the most frequently occurring allele in the population, but Val66Met is also a fairly common variation of the BDNF gene. It is this Val66Met allele that is associated with not retaining earlier learned experience about a “dangerous” environment that should be avoided.

These data suggest an intriguing explanation for some of the “wild” behavior and poor judgment to which even the smartest adolescents are prone. This kind of behavior may be based in part on the temporary forgetting in adolescence of earlier learning about which situations or environments are safe versus which ones are dangerous. Read more