Neuroscience

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Scientists Discover Area of Brain Responsible for Exercise Motivation
Scientists at Seattle Children’s Research Institute have discovered an area of the brain that could control a person’s motivation to exercise and participate in other rewarding activities – potentially leading to improved treatments for depression.
Dr. Eric Turner, a principal investigator in Seattle Children’s Research Institute’s Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain – the dorsal medial habenula – controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.  
Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression. 
“Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression,” Turner said. “But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain’s activity.” 
Dr. Turner’s study, titled “Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement,” was published today by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner’s team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington’s Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner’s genetically engineered mice also lost their preference for sweetened drinking water. 
“Without a functioning dorsal medial habenula, the mice became couch potatoes,” Turner said. “They were physically capable of running but appeared unmotivated to do it.” 
In a second group of mice, Dr. Turner’s team activated the dorsal medial habenula using optogenetics – a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could “choose” to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.  
Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula. 
“Traditional methods of stimulation could not isolate this part of the brain,” Turner said. “But cutting-edge technology at Seattle Children’s Research Institute makes discoveries like this possible.” 
As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients. 
“Working in mental health can be frustrating,” Turner said. “We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness.”

Scientists Discover Area of Brain Responsible for Exercise Motivation

Scientists at Seattle Children’s Research Institute have discovered an area of the brain that could control a person’s motivation to exercise and participate in other rewarding activities – potentially leading to improved treatments for depression.

Dr. Eric Turner, a principal investigator in Seattle Children’s Research Institute’s Center for Integrative Brain Research, together with lead author Dr. Yun-Wei (Toni) Hsu, have discovered that a tiny region of the brain – the dorsal medial habenula – controls the desire to exercise in mice. The structure of the habenula is similar in humans and rodents and these basic functions in mood regulation and motivation are likely to be the same across species.  

Exercise is one of the most effective non-pharmacological therapies for depression. Determining that such a specific area of the brain may be responsible for motivation to exercise could help researchers develop more targeted, effective treatments for depression. 

“Changes in physical activity and the inability to enjoy rewarding or pleasurable experiences are two hallmarks of major depression,” Turner said. “But the brain pathways responsible for exercise motivation have not been well understood. Now, we can seek ways to manipulate activity within this specific area of the brain without impacting the rest of the brain’s activity.” 

Dr. Turner’s study, titled “Role of the Dorsal Medial Habenula in the Regulation of Voluntary Activity, Motor Function, Hedonic State, and Primary Reinforcement,” was published today by the Journal of Neuroscience and funded by the National Institute of Mental Health and National Institute on Drug Abuse. The study used mouse models that were genetically engineered to block signals from the dorsal medial habenula. In the first part of the study, Dr. Turner’s team collaborated with Dr. Horacio de la Iglesia, a professor in University of Washington’s Department of Biology, to show that compared to typical mice, who love to run in their exercise wheels, the genetically engineered mice were lethargic and ran far less. Turner’s genetically engineered mice also lost their preference for sweetened drinking water. 

“Without a functioning dorsal medial habenula, the mice became couch potatoes,” Turner said. “They were physically capable of running but appeared unmotivated to do it.” 

In a second group of mice, Dr. Turner’s team activated the dorsal medial habenula using optogenetics – a precise laser technology developed in collaboration with the Allen Institute for Brain Science. The mice could “choose” to activate this area of the brain by turning one of two response wheels with their paws. The mice strongly preferred turning the wheel that stimulated the dorsal medial habenula, demonstrating that this area of the brain is tied to rewarding behavior.  

Past studies have attributed many different functions to the habenula, but technology was not advanced enough to determine roles of the various subsections of this area of the brain, including the dorsal medial habenula. 

“Traditional methods of stimulation could not isolate this part of the brain,” Turner said. “But cutting-edge technology at Seattle Children’s Research Institute makes discoveries like this possible.” 

As a professor in the University of Washington Department of Psychiatry and Behavioral Sciences, Dr. Turner treats depression and hopes this research will make a difference in the lives of future patients. 

“Working in mental health can be frustrating,” Turner said. “We have not made a lot of progress in developing new treatments. I hope the more we can learn about how the brain functions the more we can help people with all kinds of mental illness.”

Filed under motivation habenula exercise depression optogenetics neuroscience science

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The bit of your brain that signals how bad things could be

An evolutionarily ancient and tiny part of the brain tracks expectations about nasty events, finds new UCL research.

The study, published in Proceedings of the National Academy of Sciences, demonstrates for the first time that the human habenula, half the size of a pea, tracks predictions about negative events, like painful electric shocks, suggesting a role in learning from bad experiences.

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Brain scans from 23 healthy volunteers showed that the habenula activates in response to pictures associated with painful electric shocks, with the opposite occurring for pictures that predicted winning money.

Previous studies in animals have found that habenula activity leads to avoidance as it suppresses dopamine, a brain chemical that drives motivation. In animals, habenula cells have been found to fire when bad things happen or are anticipated.

"The habenula tracks our experiences, responding more the worse something is expected to be," says senior author Dr Jonathan Roiser of the UCL Institute of Cognitive Neuroscience. "For example, the habenula responds much more strongly when an electric shock is almost certain than when it is unlikely. In this study we showed that the habenula doesn’t just express whether something leads to negative events or not; it signals quite how much bad outcomes are expected."

During the experiment, healthy volunteers were placed inside a functional magnetic resonance imaging (fMRI) scanner, and brain images were collected at high resolution because the habenula is so small. Volunteers were shown a random sequence of pictures each followed by a set chance of a good or bad outcome, occasionally pressing a button simply to show they were paying attention. Habenula activation tracked the changing expectation of bad and good events.

"Fascinatingly, people were slower to press the button when the picture was associated with getting shocked, even though their response had no bearing on the outcome." says lead author Dr Rebecca Lawson, also at the UCL Institute of Cognitive Neuroscience. "Furthermore, the slower people responded, the more reliably their habenula tracked associations with shocks. This demonstrates a crucial link between the habenula and motivated behaviour, which may be the result of dopamine suppression."

The habenula has previously been linked to depression, and this study shows how it could be involved in causing symptoms such low motivation, pessimism and a focus on negative experiences. A hyperactive habenula could cause people to make disproportionately negative predictions.

"Other work shows that ketamine, which has profound and immediate benefits in patients who failed to respond to standard antidepressant medication, specifically dampens down habenula activity," says Dr Roiser. "Therefore, understanding the habenula could help us to develop better treatments for treatment-resistant depression."

(Source: eurekalert.org)

Filed under habenula negative events dopamine ketamine experiences neuroscience science

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