brain circuit

Scientists Find A Brain Circuit That Could Explain Seasonal Depression

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Before light reaches these rods and cones in the retina, it passes through some specialized cells that send signals to brain areas that affect whether you feel happy or sad.

 

Just in time for the winter solstice, scientists may have figured out how short days can lead to dark moods.

Two recent studies suggest the culprit is a brain circuit that connects special light-sensing cells in the retina with brain areas that affect whether you are happy or sad.

When these cells detect shorter days, they appear to use this pathway to send signals to the brain that can make a person feel glum or even depressed.

“It’s very likely that things like seasonal affective disorder involve this pathway,” says Jerome Sanes, a professor of neuroscience at Brown University.

Sanes was part of a team that found evidence of the brain circuit in people. The scientists presented their research in November at the Society for Neuroscience meeting. The work hasn’t been published in a peer-reviewed journal yet, but the researchers plan to submit it.

A few weeks earlier, a different team published a study suggesting a very similar circuit in mice.

Together, the studies offer a strong argument that seasonal mood changes, which affect about 1 in 5 people, have a biological cause. The research also adds to the evidence that support light therapy as an appropriate treatment.

“Now you have a circuit that you know your eye is influencing your brain to affect mood,” says Samer Hattar, an author of the mouse study and chief of the section on light and circadian rhythms at the National Institute of Mental Health. The finding is the result of a decades-long effort to understand the elusive link between light and mood. “It is the last piece of the puzzle,” Hattar says.

The research effort began in the early 2000s, when Hattar and David Berson, a professor of neuroscience at Brown University, were studying cells in the retina.

Researchers Uncover A Circuit For Sadness In The Human Brain

At the time, most scientists thought that when light struck the retina, only two kinds of cells responded: rods and cones. But Hattar and Berson thought there were other light-sensitive cells that hadn’t been identified.

“People used to laugh at us if we say there are other photoreceptors distinct from rods and cones in the retina,” Hattar says.

The skeptics stopped laughing when the team discovered a third kind of photoreceptor that contained a light-sensitive substance called melanopsin not found in rods and cones. (The full name of these cells, if you’re interested, is intrinsically photosensitive retinal ganglion cells, or ipRGCs.) These receptors responded to light but weren’t part of the visual system.

Instead, their most obvious function was keeping the brain’s internal clock in sync with changes in daylight. And many scientists assumed that this circadian function also explained seasonal depression.

“People thought that the only reason you get mood problems is because your clock is misaligned,” Hattar says.

Other potential explanations included speculation that reduced sunlight was triggering depression by changing levels of serotonin, which can affect mood, or melatonin, which plays a role in sleep patterns and mood. But the evidence for either of these possibilities has been weak.

Hattar and Berson were pretty sure there was a better reason. And, after years of searching, they found one.

In September, Hattar’s team published a study about mice suggesting a direct pathway between the third kind of photoreceptor in the retina and brain areas that affect mood.

When these cells were present, an artificially shortened cycle of light and dark caused a version of depression in a mouse. But when the team removed the cells with gene-editing tools, the mouse didn’t become depressed.

Sanes knew about the research, in part because he and Berson are neuroscientists at Brown. And he was so intrigued by the discovery of the new pathway between retina and brain in mice that he decided to see whether something similar was going on in human brains.

Sanes’ team put young adults in an MRI machine and measured their brain activity as they were exposed to different levels of light. This allowed the team to identify brain areas that seemed to be receiving signals from the photoreceptors Hattar and Berson had discovered.

Two of these areas were in the front of the brain. “It’s interesting because these areas seem to be the areas that have been shown in many studies to be involved in depression and other affective disorders,” Sanes says.

The areas also appeared to be part of the same circuit found in mice.

The finding needs to be confirmed. But Hattar is pretty confident that this circuit explains the link between light exposure and mood.

So now he’s trying to answer a new question: Why would evolution produce a brain that works this way?

“You will understand why you would need light to see,” he says, “but why do you need light to make you happy?”

Hattar hopes to find out. In the meantime, he has some advice for people who are feeling low: “Try to take your lunch outside. That will help you adjust your mood.”

Scientists pinpoint brain circuit for risk preference in rats

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The researchers focused on a complex of brain circuitry known as the reward system that is shared by every living creature from flies to humans. This circuitry’s evolutionary conservation is due to its essential role in guiding individuals’ behavior, and ensuring species’ survival, by inducing pleasurable sensations and boosting motivation in response to the anticipation or realization of behaviors such as eating and mating.

Investigators at Stanford University have identified a small group of nerve cells in a specific brain region of rats whose signaling activity, or lack of it, explains the vast bulk of differences in risk-taking preferences among the animals.

That activity not only predicts but effectively determines whether an animal decides to take a chance or stick with the safe choice.

The findings expand on noninvasive research conducted previously in humans. “Humans and rats have similar brain structures involved,” said Karl Deisseroth, MD, PhD, professor of bioengineering and of psychiatry and behavioral sciences. “And we found that a drug known to increase risk preference in people had the same effect on the rats. So every indication is that these findings are relevant to humans.

“Risky behavior has its moments where it’s valuable,” he added. “As a species, we wouldn’t have come as far as we have without it.”

But a propensity for high-risk behavior can be damaging, too, said Deisseroth, a practicing psychiatrist. “I’ve seen patients whose aberrantly high-risk-seeking activity resulted in accidents, addictions and social, financial or occupational failures that exposed them to a lot of harm and blame.”

The research is described in a paper to be published online March 23 inNature. Deisseroth is the senior author. The lead author is graduate student Kelly Zalocusky.

By throwing light not only on how individual decisions are made but on why individuals differ in their overall risk-taking profiles, the study could provide a better understanding of some psychiatric conditions and lead to better medications to treat them. And, for that matter, it could help researchers mitigate the effect of drugs that themselves influence risk preferences. For example, a drug called pramipexole, prescribed for Parkinson’s disease and other brain disorders, can cause gambling problems.

Appetite for risk varies

Individuals vary in their appetite for risk, said Deisseroth, the D.H. Chen Professor and a Howard Hughes Medical Institute investigator. Most adult humans are relatively risk-averse. Given a choice between, say, a stable salary or fluctuating freelance income that’s likely to wind up being about the same or even somewhat larger in the long run, individuals will usually pick the salaried option.

That makes evolutionary sense, Deisseroth said. “One can’t always take the long view. In an always-changing world filled with dangers ranging from starvation to predators, even if a riskier option has a higher expected return over time, one can’t always live long enough to take advantage of it,” he said.

However, a minority within each species studied tends to prefer risk. And even largely risk-averse individuals sometimes choose riskier options.

The researchers focused on a complex of brain circuitry known as the reward system that is shared by every living creature from flies to humans. This circuitry’s evolutionary conservation is due to its essential role in guiding individuals’ behavior, and ensuring species’ survival, by inducing pleasurable sensations and boosting motivation in response to the anticipation or realization of behaviors such as eating and mating.

Reward system’s key nerve tract

A core feature of the reward system is a nerve tract projecting from a deep-brain structure called the ventral tegmental area to another structure in the forebrain, the nucleus accumbens. Nerve cells in this tract can secrete a chemical called dopamine that binds to surface receptors residing on some nerve cells in the nucleus accumbens. This, in turn, ignites activity within the cells that harbor dopamine-receptors. The receptors fall mainly into two categories, DR1 and DR2, that are mostly found on different cells.

Drawing on hints from the medical literature — including previous human brain-imaging research by study co-author and associate professor of psychology Brian Knutson, PhD, indicating increased activity in the nucleus accumbens when people were considering taking risks — the researchers zeroed in on activity in DR2-containing nerve cells in the nucleus accumbens during the decision-making process. They used a single, hair-thin optical fiber implanted in the rats’ nucleus accumbens to both monitor electrochemical signals there — a technique called fiber photometry — and precisely duplicate these naturally occurring signals’ timing and magnitude by stimulating cells with light — a technique called optogenetics. Both techniques were pioneered in Deisseroth’s lab.

The scientists targeted DR2 cells in rats that had been trained and fitted for both fiber photometry and optogenetics with a thin, implanted optical fiber that allowed the rats to move freely. The experiments that followed were designed by Zalocusky and her colleagues including Knutson and Deisseroth.

Mmmmm, sugar water

The rats could initiate a session by poking their nose into a hole, at which point two levers would pop out. Pulling one lever, the rats soon learned, resulted in a dependable dose of sugar water, always the same size. Pulling the other lever would yield a much smaller sugar-water dose most of the time, but a much larger one every so often. The system was set up so that either lever would earn a rat the same total payoff, eventually.

Once trained, about two-thirds of the rats proved risk-averse, consistently choosing the steady-paying “salary.” The remaining one-third were risk-seeking “freelance” types. If the researchers tricked the rats by reversing the levers’ payoffs, the rats responded by switching levers, each adhering to its own preferred reward schedule.

Occasionally, though, a rat of either type would check out the neglected option. If a risk-averse rat experimenting in this fashion happened to get lucky and reap a windfall, it would try that lever again; if it received a pittance, it quickly returned to the “salary” lever. The easy-come, easy-go risk-seekers were relatively unfazed by smaller-than-anticipated rewards. Like some people, a risk-seeking rat on a losing streak doesn’t give up so easily.

Altering rats’ risk preferences

Fiber-photometric observation indicated that — during a roughly 1-second period after a rat initiated the trial but before it was allowed to pull one or the other lever — activity in DR-2-containing nerve cells of the nucleus accumbens was significantly elevated in risk-averse, but not risk-seeking, rats. Mimicking this signaling pattern by optogenetically stimulating DR-2 cells with laser-light pulses, the researchers caused risk-seeking rats to become risk-averse. Their gambling penchant returned as soon as the laser pulses were halted. Stimulating the same cells in rats that were already risk-averse produced essentially no change in their behavior.

In contrast, delivering pramipexole (a DR2-stimulating drug that promotes risky behavior in people) directly to the rats’ nucleus accumbens temporarily converted risk-avoider rats into risk-seekers and also reduced the signal’s size in their nucleus accumbens. A DR1-stimulating compound had no such effect.

“It looks as though we have found a brain signal that, in most individuals, corresponds to a memory of a failed risky choice,” said Deisseroth. “It seems to represent the memory of that recent unfavorable outcome, manifested later at just the right time when it can, and does, modify an upcoming decision.”

The signal was highest in risk-averse rats that had been dealt a disappointing outcome on the previous trial, and was weak in risk-seeking rats, unless forced into existence by optogenetic stimulation. This signal could serve as a guide for understanding interpersonal variability in risk-seeking. “It also might be possible to use this animal assay to predict how different drugs can influence human risk-taking,” Zalocusky said.

Scientists Now Know How Your Brain Wakes You Up

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Neuroscientists discover a brain circuit responsible for rapid waking.

Recent research has made huge strides in demystifying sleep — why we need it,how to get more of it, and what happens when we don’t get enough of it. But there’s still a lot that remains largely unknown, including the way brain circuits control the sleep-wake cycle. Until now, that is.

In a landmark study, neuroscientists at the University of Bern in Switzerland discovered a pattern of brain activity that is responsible for waking us up from light sleep and anesthesia.

“These findings identify a new network and refine our understanding of the brain network that regulates sleep and wake cycle,” Dr. Antoine Adamantidis, a neuroscientist at the university and the study’s lead author, told The Huffington Post in an email.

The study, which was published on Dec. 21 in the journal Nature Neuroscience, showed that activating the circuit associated with the rhythms of electrical activity that occur during sleep — which is located between the hypothalamus and thalamus brain regions — causes rapid wakefulness. While, inhibiting the circuit deepens sleep.

For the study, the researchers used a new technique called “optogenetics” on mice, inserting light-reactive genes into certain neurons in the rodents’ circuit and then “turning on” those neurons via light pulses.

When the researchers activated the neurons in the circuit, they were able to induce rapid awakening from sleep. And when they stimulated these neurons for an extended period, the mice stayed awake. However, when the researchers inhibited the neurons in the circuit, the mice slept longer, more intensely, and with fewer interruptions.

What’s more, the arousing power of this brain circuit was so strong that it even led the mice to regain consciousness after being put under anesthesia.

Adamantidis called the discovery “exciting” as it could lead to new methods for therapeutical approaches to waking someone from a vegetative or minimally conscious state. So far, such methods have been limited.

The researchers say the new discovery may also lead to more targeted treatments for insomnia or sleep disturbances, once they are able to determine how malfunctions in the brain circuit are related to sleep issues.

“It’s a big question in the field,” Adamantidis said. “Possibly those circuits may become hypersensitive to certain inputs, so their hyperactivity may delay the sleep onset, and may also results in fragmented sleep — two hallmarks of insomnia.”