Strong emotions such as fear and anxiety tend to be accompanied and reinforced by measurable bodily changes including increased blood pressure, heart rate and respiration, and dilation of the eyes’ pupils. These so-called “physiological arousal responses” are often abnormally high or low in psychiatric illnesses such as anxiety disorders and depression. Now scientists at the UNC School of Medicine have identified a population of brain cells whose activity appears to drive such arousal responses.
The scientists, whose study is published in Cell Reports, found that artificially forcing the activity of these brain cells in mice produced an arousal response in the form of dilated pupils and faster heart rate, and worsened anxiety-like behaviors.
The finding helps illuminate the neural roots of emotions, and point to the possibility that the human-brain counterpart of the newly identified population of arousal-related neurons might be a target of future treatments for anxiety disorders and other illnesses involving abnormal arousal responses.
“Focusing on arousal responses might offer a new way to intervene in psychiatric disorders,” said first author Jose Rodríguez-Romaguera, PhD, assistant professor in the UNC Department of Psychiatry and member of the UNC Neuroscience Center, and co-director of the Carolina Stress Initiative at the UNC School of Medicine.
Rodríguez-Romaguera and co-first author Randall Ung, PhD, an MD-PhD student and adjunct assistant professor in the Department of Psychiatry, led this study when they were members of the UNC laboratory of Garret Stuber, PhD, who is now at the University of Washington.
“This work not only identifies a new population of neurons implicated in arousal and anxiety, but also opens the door for future experiments to systematically examine how molecularly defined cell types contribute to complex emotional and physiological states,” Stuber said. “This will be critical going forward for developing new treatments for neuropsychiatric disorders.”
Anxiety disorders, depression, and other disorders featuring abnormally high or low arousal responses affect a large fraction of the human population, including tens of millions of adults in the United States alone. Treatments may alleviate symptoms, but many have adverse side effects, and the root causes of these disorders generally remain obscure.
Untangling these roots amid the complexity of the brain has been an enormous challenge, one that laboratory technology has only recently begun to surmount.
Rodríguez-Romaguera, Ung, Stuber and colleagues examined a brain region within the amygdala called the BNST (bed nucleus of the stria terminalis), which has been linked in prior research to fear and anxiety-like behaviors in mice.
Increasingly, scientists view this region as a promising target for future psychiatric drugs. In this case, the researchers zeroed in on a set of BNST neurons that express a neurotransmitter gene, Pnoc, known to be linked to pain sensitivity and more recently to motivation.
The team used a relatively new technique called two-photon microscopy to directly image BNST Pnoc neurons in the brains of mice while the mice were presented with noxious or appealing odors — stimuli that reliably induce fear/anxiety and reward behaviors, respectively, along with the appropriate
Scientists say they have spotted the gene responsible for telling you when it’s time to pee.
The gene, called PIEZO2, may help at least two different types of cells sense when the bladder is full and needs to be emptied.
“Urination is essential for our health. It’s one of the primary ways our bodies dispose of waste. We show how specific genes and cells may play critical roles in initiating this process,” said study senior author Ardem Patapoutian, a professor at the Scripps Research Institute, in La Jolla, Calif. “We hope that these results provide a more detailed understanding of how urination works under healthy and disease conditions.”
The study, which was funded by the U.S. National Institutes of Health and included NIH researchers, was published recently in the journal Nature.
The PIEZO2 gene has instructions for making proteins that are activated when cells are stretched or squeezed. The researchers found that patients who are born with a genetic deficiency in PIEZO2 have trouble sensing when their bladder is full, and experiments in mice suggest the gene has two roles in this process.
According to study lead author Kara Marshall, “There were a lot of reasons to think that PIEZO2 could be important for urination. Theoretically, it made sense as it is a pressure sensor for other internal sensory processes.” Marshall is a postdoctoral researcher at Scripps.
In 2015, researchers discovered people who were born with mutations in their PIEZO2 genes. They had no sense of the movement of the body and could not feel some types of touch and pain. They also had something else in common, the study authors said in an NIH news release.
“We were really struck by what we heard during background interviews with patients and their families,” said researcher Dr. Dimah Saade, a clinical fellow at the NIH. “Almost everyone mentioned that the patients had problems with urination. As children, they had trouble potty training. They would often have urinary tract infections. And most of them follow a daily urination schedule. After seeing a consistent pattern, we decided to take a closer look.”
Almost all of the patients said they could go all day without feeling the need to urinate, and most urinated less than the normal five to six times per day.
Marshall said, “These results strongly suggested that PIEZO2 plays a role in urination. We wanted to know how it may do this.” Experiments in mice helped find the answer.
The researchers found that the PIEZO2 gene was highly active in a few neurons that send nerve signals from the mouse bladder to the brain. Aided by an imaging system, they saw that the cells lit up with activity when a mouse’s bladder filled.
“These were the first clues to understanding wherein the urinary tract PIEZO2 worked. They suggested that it may help control the bladder,” said researcher Nima Ghitani, a postdoctoral fellow at the NIH.
For more on urination, head to the U.S. National Library of Medicine.
Oct. 22 (UPI) — Researchers have developed a simple blood test to identify pancreatic cancers that are more likely to respond to treatment than others, according to a paper published Thursday by Clinical Cancer Research.
The test detects and measures the levels of a sugar called sTRA, which is produced by some types of pancreatic cancer and escapes into the bloodstream. Pancreatic cancers that produce sTRA often do not respond to chemotherapy, the researchers said.
Testing prostate cancer patients for sTRA one day could guide treatment decisions, sparing patients with untreatable cancers from undergoing unnecessary therapies and experiencing potential side effects.
“Knowing which type of pancreatic cancer a person has is critical to implementing the right treatment strategy for each patient,” one of the researchers, Brian Haab, said in a statement.
“We hope that our new test, which detects a marker produced by cancer cells of one subtype and not the other, will one day soon be a powerful tool to help physicians and patients make the best decisions possible,” said Haab, a professor at the Van Andel Institute in Michigan.
About 60,000 people in the United States are diagnosed with pancreatic cancer annually and nearly 50,000 people die from it each year, according to the National Cancer Institute.
Pancreatic cancers are among the most challenging malignancies to treat, due in part to their ability to evade detection until they have advanced and spread.
No reliable way exists to determine whether a patient has a type of pancreatic cancer that will respond to existing chemotherapies, and the result often is a blanket treatment approach that works in some patients but can leave all with troubling side effects.
The new sTRA test evolved from an earlier test that combined an existing diagnostic approach designed to detect a sugar called CA19-9 with a new one that detected sTRA.
The combination approach detected nearly 70% of pancreatic cancers with a less than 5% false-positive rate — roughly 30% more than the CA19-9 alone, the researchers said.
Both the combination test and the new sTRA test still need to undergo further clinical studies to confirm their accuracy, they said.
“The … combination test tells us whether there is cancer, and the new sTRA test helps us determine what kind of pancreatic cancer, which then could allow physicians to better narrow down the appropriate treatment plan,” Haab said.
“When used in sequence, we believe the combination test and the new sTRA test could help catch and identify pancreatic cancer more quickly and definitively,” he said.
In the ferocious arena of a northern elephant seal colony, where few males ever get to mate, jostling suitors often face bloody battles over access to groups of females. And these boisterous bulls have a dramatic way of making their presence known to rivals: individuals identify themselves via rhythmic, guttural calls, accompanied by body slams that literally shake the ground around them.
Now research indicates that the seals are not born with these identifying signals. Rather they develop their unique brands of vocal bravado as they age, according to a recent paper published in Animal Behaviour.
The researchers recorded more than 440 calls from 47 male elephant seals at various stages of development in California’s Año Nuevo State Park. In this colony of 2,000 animals, a dominant male may vie with 50 top competitors—each of whom possesses his own call. These vocalizations develop around the same time as the seals carve out jealously guarded territories of about 20 square meters.
Less established younger males, in contrast, are “acoustically inconspicuous” and produce short, unstructured calls. They seem to avoid standing out, which may help them gain time to mature, says lead author Caroline Casey, a graduate student in ecology and evolutionary biology at the University of California, Santa Cruz. At around the age of eight or nine, the seals finally settle on a personal song.
“It’s really when they have a shot at reproducing and becoming socially competitive that these signature calls start to emerge,” Casey says.
The resulting recognition comes in handy, as male seals appear to listen for—and avoid—individuals who have previously bested them in fights. Instead they target their competitive energies toward bulls with whom they know they are more evenly matched.
Casey suspects that the ruthless nature of male elephant seal society is what prompts the development of individualistic vocalizations. To explore that difficult-to-prove connection, she says, she would like to also analyze seal calls from less tightly packed communities, which could be less competitive.
Luke Rendell, a biologist in the Sea Mammal Research Unit at the University of St Andrews in Scotland, who was not involved in the study, agrees that this motivation is a possibility. Rival seals’ ability to acoustically differentiate themselves from one another may even be something they learn from their elders around the point of reaching sexual maturity, he suggests.
“My hunch is that there is some learning involved,” Rendell says. He praises the study for including enough data from seals in different age groups to clearly show the transition from indistinct to distinct calls: “I thought it was a really significant contribution.”