Navigation Links
Gene controls whether fear is a factor

In the Nov. 18 issue of Cell, researchers report the discovery of a gene that controls the ability to react with appropriate fear to impending danger. As a result, mice lacking the gene stathmin become daredevils of a sort, the researchers report. The basic findings may have general implications for the study of anxiety disorders and potential anti-anxiety drugs, according to researchers.

The researchers found that the gene stathmin--normally present in high levels in a part of the brain called the amygdala--controls both innate and learned fear. Mice without the gene show abnormally low levels of anxiety in situations that should instinctively inspire fear. Stathmin-deficient animals also show less reaction to conditions that have previously proven unpleasant, an indication that the mice lack a normal memory for fear.

"While one of the best understood memory-related neural circuitries within the mammalian brain is that which controls fear conditioning, little is known about the molecular mechanisms underlying fear reactions," said lead author of the study by Gleb Shumyatsky of Rutgers University. "We have now found that stathmin plays a critical role in both learned and innate fear. Knockout mice, which lack the gene, show a decreased memory for fear and fail to recognize danger in innately aversive environments."

By contrast, he added, the mice depleted of stathmin perform normally in a test of spatial learning.

Fear reactions represent a spectrum of behaviors that vary from those that are inborn to those instilled through experience, said the researchers. Instinctive fears--such as fear of heights or predators--are often species specific toward actual or potential threats. In contrast, learned fear results from particular uncomfortable or life-threatening events in the past.

Because fear plays an essential role in survival, memory for fear is easily established, very resistant to extinction, and normally lasts a lifetime, Sh umyatsky said.

In the laboratory, fear can be conditioned by linking a neutral stimulus, such as a light or sound, to something unpleasant or painful, such as an electric shock, he explained. That process of learned association occurs in a portion of the amygdala called the lateral nucleus.

As a first step to unravel the molecular events underlying fear learning, Shumyatsky's group recently identified several genes present at particularly high levels in the lateral nucleus and in the structures that relay information about learned and instinctive fear to the amygdala. One such gene was stathmin.

In the current study, the researchers found that the brains of mice lacking stathmin showed an unusual number of microtubules, which are structural components of the cytoskeleton. Stathmin normally controls the assembly and breakdown of the cellular scaffolds, Shumyatsky explained.

"For memory, the brain needs to quickly disassemble and rebuild microtubules to form connections where they are needed," Shumyatsky said. "It appears that loss of stathmin might interfere with this ability in the amygdala, leading to the overproduction of microtubules in certain areas. In essence, the cells lose their flexibility."

Indeed, the researchers found impairments in the ability of key inputs in the animals' brains to form connections between neurons. Such connections form the cellular basis for learning and memory.

To relate these brain abnormalities to behavior, the team then exposed normal and stathmin-deficient mice to a neutral tone while delivering a mild electric shock. While both groups displayed some fear response by freezing immediately after a shock and later after hearing the tone, knockout mice reacted less strongly, they found, suggesting that they had an impaired ability to learn fear.

In other tests, the mutant mice also showed less instinctive fear of open spaces, venturing out into environments they would usually av oid naturally, Shumyatsky said. Mice lacking stathmin continued to perform normally on a water maze test, an indication that spatial learning and memory--controlled outside of the amygdala--were unaltered.

"The findings provide genetic evidence that amygdala-enriched stathmin is required for the expression of innate fear and the formation of memory for learned fear," Shumyatsky said.

"This evidence suggests that stathmin knockout mice can be used as a model of anxiety states of mental disorders with innate and learned fear components," he added. "As a corollary, these animal models could be used to develop new anti-anxiety agents."

Together with the team's earlier findings that the amygdala-enriched gene gastrin-releasing peptide selectively affects learned fear, the new findings support the clinical data suggesting that anxiety is a spectrum of disorders with multiple subclasses, each of which may have a unique molecular signature requiring distinctive approaches to therapy, the researchers said.


'"/>

Source:Cell Press


Related biology news :

1. Cooperation is key—a new way of looking at MicroRNA and how it controls gene expression
2. Master gene controls healing of skin in fruit flies and mammals
3. Scientists find that protein controls aging by controlling insulin
4. MicroRNA tweaks protein that controls early heart development
5. Scientists discover gene that controls speed of tuberculosis development
6. Salk researchers make fast strides towards understanding how our body controls walking
7. Robotic joystick reveals how brain controls movement
8. What controls stickiness of smart chromosomal glue
9. Molecular on/off switch controls immune defenses against viruses
10. Pair of microRNA molecules controls major oncogene in most common leukemia
11. Fast and slow -- How the spinal cord controls the speed of movement
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/2/2016)... Va. , Feb. 2, 2016   ... award from the U.S. Army Research Office and ... the range and sensitivity of the company,s ... Past Accounting Mission and, more generally, defense-related DNA ... DNA phenotyping capabilities (predicting appearance and ancestry from ...
(Date:1/28/2016)... -- Synaptics (NASDAQ: SYNA ), a leading developer of human ... December 31, 2015. --> --> ... 2 percent compared to the comparable quarter last year to $470.5 ... $35.0 million, or $0.93 per diluted share. ... quarter of fiscal 2016 grew 9 percent over the prior year ...
(Date:1/22/2016)... 22, 2016 ... the "Global Biometrics Market in Retail ... --> http://www.researchandmarkets.com/research/p74whf/global_biometrics ) has ... Biometrics Market in Retail Sector 2016-2020" ... Research and Markets ( http://www.researchandmarkets.com/research/p74whf/global_biometrics ) ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... Feb. 3, 2016 Ascendis Pharma A/S (Nasdaq: ... applies its innovative TransCon technology to address significant unmet ... upcoming investor conference.Event:2016 Leerink Partners Global Healthcare Conference Location: ... Wednesday, February 10, 2016 Time:  , 11:55am EST ... --> An audio webcast of this event ...
(Date:2/3/2016)... 3, 2016 New Jersey Health Foundation (NJHF) ... million for researchers in New Jersey ... that demonstrates exciting potential.   James ... the New Jersey Health Foundation Research Grant Program ... educational institutions— Princeton University, Rutgers University, Rowan University ...
(Date:2/3/2016)... ... February 03, 2016 , ... ProMIS ... potential targets (epitopes) specific to misfolded, propagating strains of Amyloid beta involved in ... antibody therapeutics for Alzheimer’s. , Following on from the first misfolded Amyloid beta ...
(Date:2/3/2016)... ... February 03, 2016 , ... ... report which summarizes and analyzes nearly 750 unique supply chain notifications and ... analysis service. , Supply chain risk management practitioners subscribe to the EventWatch ...
Breaking Biology Technology: