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September 7, 2018

Researchers Identify Key Brain Circuits for Reward-Seeking, Avoidance Behavior

Researchers have identified connections between neurons in brain systems associated with reward, stress and emotion. Conducted in mice, the new study may help untangle multiple psychiatric conditions, including alcohol use disorder, anxiety disorders, insomnia and depression in humans.

“Understanding these intricate brain systems will be critical for developing diagnostic and therapeutic tools for a broad array of conditions,” said Dr. George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, which contributed funding for the study. NIMH also provided major support for the research.

A report of the study, by first author Dr. William Giardino and colleagues at Stanford University, appeared in the August 2018 issue of Nature Neuroscience.

Responding appropriately to aversive or rewarding stimuli is essential for survival. This requires fine-tuned regulation of brain systems that enable rapid responses to changes in the environment, such as those involved in sleep, wakefulness, stress and reward-seeking. These same brain systems are often dysregulated in addiction and other psychiatric conditions.

In the new study, researchers looked at the extended amygdala, a brain region involved in fear, arousal and emotional processing and which plays a significant role in drug and alcohol addiction. They focused on a part of this structure known as the bed nucleus of stria terminalis (BNST), which connects the extended amygdala to the hypothalamus, a brain region that regulates sleep, appetite and body temperature.

The hypothalamus is also thought to promote both negative and positive emotional states. A better understanding of how the BNST and hypothalamus work to coordinate emotion-related behavior could shed light on the emotional processes dysregulated in addiction.

That Stinks! 1 in 15 Americans Smell Odors That Aren’t There

Woman covering her nose for bad smell

Imagine the foul smell of an ash tray or burning hair. Now imagine if these kinds of smells were present in your life, but without a source. A new study finds that 1 in 15 Americans (or 6.5 percent) over the age of 40 experiences phantom odors. The study, published in JAMA Otolaryngology-Head and Neck Surgery, is the first in the U.S. to use nationally representative data to examine the prevalence of and risk factors for phantom odor perception. The study could inform future research aiming to unlock the mysteries of phantom odors.

The study was led by Dr. Kathleen Bainbridge of the Epidemiology and Biostatistics Program at NIDCD. She and her team used data from 7,417 participants over 40 years of age from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The NHANES data were collected by the National Center for Health Statistics, which is part of the Centers for Disease Control and Prevention; data collection was partly funded by NIDCD.

“Problems with the sense of smell are often overlooked, despite their importance. They can have a big impact on appetite, food preferences and the ability to smell danger signals such as fire, gas leaks and spoiled food,” said Dr. Judith A. Cooper, acting NIDCD director.

Dr. Donald Leopold, one of the study’s authors and clinical professor in the department of surgery at the University of Vermont Medical Center, adds that patients who perceive strong phantom odors often have a miserable quality of life and sometimes cannot maintain a healthy weight.

The ability to identify odors in the environment is known to decrease with age. This study found that the prevalence of phantom odor perception also decreases with age and, interestingly, is not related to individuals’ ability to correctly identify odors.

Researchers Find Potential New Gene Therapy for Blinding Disease

Blind man talking on a cellphone

Scientists funded by the National Eye Institute report a novel gene therapy that halts vision loss in a canine model of a blinding condition called autosomal dominant retinitis pigmentosa (adRP). The strategy could one day be used to slow or prevent vision loss in people with the disease.

“We’ve developed and shown proof-of-concept for a gene therapy for one of the most common forms of retinitis pigmentosa,” said Dr. William Beltran of the University of Pennsylvania School of Veterinary Medicine, a lead author of the study, which appeared online Aug. 20 in the Proceedings of the National Academy of Sciences.

Retinitis pigmentosa refers to a group of rare genetic disorders that damage light-sensing cells in the retina known as photoreceptors. Rod photoreceptor cells enable vision in low light and require a protein called rhodopsin for their light-sensing ability. People with adRP caused by mutations in the rhodopsin gene usually have one good copy of the gene and a second, mutated copy that codes for an abnormal rhodopsin protein. The abnormal rhodopsin is often toxic, slowly killing the rod cells. As the photoreceptors die, vision deteriorates over years or decades. Scientists have identified more than 150 rhodopsin mutations that cause adRP, challenging efforts to develop effective therapies.

The research team generated a gene therapy construct that knocks down the rod cells’ ability to produce rhodopsin using a technology known as shRNA (short-hairpin RNA) interference.

Gene therapy introduces genetic material, like shRNA, into cells to compensate for abnormal genes or to make a beneficial protein. Often adapted from viruses, vectors are engineered to effectively deliver this genetic material into cells without causing disease.

“The beauty of this novel gene therapy product is in its elegant vector design. I hope it works as well in humans, too,” said Dr. Neeraj Agarwal, translational research program director at NEI.

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