Brain circuit can tune anxiety

New findings may help neuroscientists pinpoint better targets for antianxiety treatments.

Anxiety disorders, which include posttraumatic stress disorder, social phobias, and obsessive-compulsive disorder, affect 40 million American adults in a given year. Currently available treatments, such as antianxiety drugs, are not always effective and have unwanted side effects.

To develop better treatments, a more specific understanding of the brain circuits that produce anxiety is necessary, says Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.

“The targets that current antianxiety drugs are acting on are very nonspecific. We don’t actually know what the targets are for modulating anxiety-related behavior,” Tye says.

In a step toward uncovering better targets, Tye and her colleagues have discovered a communication pathway between two brain structures — the amygdala and the ventral hippocampus — that appears to control anxiety levels. By turning the volume of this communication up and down in mice, the researchers were able to boost and reduce anxiety levels… Original Article »

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From the frontline: 30 something science

What’s being female got to do with anything, ask the scientists who are starting labs and having kids.

Being five months pregnant comes with a series of concessions: no booze, no sushi, no double-shot espressos. Less appreciated, perhaps, is the havoc it can wreak on a breakdancer’s moves. “My dancing is definitely limited now,” says Kay Tye, neurobiologist, award-winning b-girl and assistant professor at the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology (MIT) in Cambridge. “I can’t do windmills — I can’t do anything that might cause me to fall. Which is, like, everything.”

It is one of the few limitations that Tye, 31, has been willing to accept. Striving to make her mark in optogenetics, one of the hottest fields in neuroscience, Tye thought nothing of working past midnight, getting by on four or five hours sleep a night and maintaining a constant, transcontinental travel schedule. She has had to dial back a little in recent weeks, and she knows that life may change further once her daughter is born. But she is ready. “I’ve been preparing for this my entire life,” she says. “I chose a career path that’s family friendly.”

An assistant professorship at MIT, where the tenure rate hovers at around 50% and the faculty is still about 80% male, may not strike many as particularly family friendly. But Tye, the daughter of a theoretical-physicist father and a biochemist mother, grew up in her mother’s lab, where she was paid 25 cents per box to rack pipette tips. With her mother as a role model, Tye says that she was in her teens before it occurred to her that her gender could hold back her career. “And by then, my brain was already fully formed,” she says with a smile… Original Article »

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Depression Eraser

Stimulating dopamine-releasing neurons immediately extinguishes depression in mice.

MIT and Stanford University researchers recently pinpointed brain cells that could be new targets for treating depression, which affects an estimated one in 10 Americans. By stimulating these cells to deliver dopamine to other parts of the brain, the researchers were able to immediately eliminate symptoms of depression in mice. They also induced depression in normal mice by shutting off the dopamine source.

“The first step to achieving a new era of therapy is identifying targets like these,” says Kay Tye, an assistant professor of brain and cognitive sciences at MIT and a member of MIT’s Picower Institute for Learning and Memory. She says she hopes the fact that this target exists “motivates drug companies to revitalize their neuroscience research groups.”

Many depressed patients are prescribed drugs, including Prozac, that boost the brain chemical serotonin. However, these require four to six weeks to take effect, suggesting that serotonin may not be part of the brain system most responsible for depression-related symptoms, Tye says. Finding more specific targets, rather than dousing the whole brain in chemicals, is the key to developing better therapies, she believes… Original Article »

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Looking at a Bright Future: Optogenetics in your Lab

Have you heard about optogenetics yet? If not, you soon will. Optogenetics techniques are sweeping neuroscience research. Named as the Method of the Year in 2010 by Nature Methods, optogenetics techniques are becoming widespread.

The reason is clear: optogenetics offers the unprecedented ability to manipulate specific cells in real-time in freely behaving animals essentially by controlling a light switch. This allows for the dissection of intricate microcircuits that was previously impossible.  Specific brain regions and neuronal types can be turned on and off at will. The effect on animal behavior of activation of a specific neuronal circuit can be observed immediately. This is an exciting and far-reaching opportunity to fine-tune functional and neuroanatomical knowledge.

The technology began as the result of long-time collaborations between Drs. Edward Boyden and Karl Deisseroth, among others (Boyden 2011).  To better define the roles of individual neurons, these pioneers sought a way to drive or silence specific neurons embedded in intact brain circuitry.  They found the way using an ion channel expressed in the green algaChlamydomonas reinhardtii: channelrhodopsin-2 (ChR-2).  ChR-2 is a cation-selective ion channel that is directly light-gated.  In green alga, ChR-2serves to direct the alga to or from a light source to facilitate photosynthesis (Sineshchekov et al., 2002).  When inserted into neurons, ChR-2 mediates light-driven spiking (Boyden et al., 2005).  Viral transfection was first used to successfully express ChR-2 in neurons in vivo, thus opening the field of optogenetics to animal models (Arenkiel et al., 2007)… Original Article »

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Dissecting the Neural Circuits Mediating Anxiety

Neurostimulation as a tool for Basic Science and Medicine. 

Anxiety disorders are the single most common class of psychiatric diseases, afflicting up to 28% of the adult population. Although human imaging studies have implicated the amygdala in anxiety, little is known about the functional role of individual microcircuits and distal circuits in terms of their individual contributions to anxiety. Optogenetics, the use of genetically-encodable, light-activated proteins that can be used to depolarize or hyperpolarize cell membranes, is a quickly-growing field. We developed optogenetic projection-specific targeting, electrophysiological and imaging techniques to parse the different circuit contributions, and we apply this multidisciplinary approach to provide a complete view of how amygdala interactions with the rest of the brain can govern anxiety-related behaviors… Original Video »

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An On-Off Switch for Anxiety

Researchers discover a brain circuit that can instantly dampen—or exacerbate—anxiety in mice.

With the flick of a precisely placed light switch, mice can be induced to cower in a corner in fear or bravely explore their environment. The study highlights the power of optogeneticstechnology—which allows neuroscientists to control genetically engineered neurons with light—to explore the functions of complex neural wiring and to control behavior.

In the study, Karl Deisseroth and collaborators at Stanford University identified a specific circuit in the amygdala, a part of the brain that is central to fear, aggression, and other basic emotions, that appears to regulate anxiety in rodents. They hope the findings, published today in the journal Nature, will shed light on the biological basis for human anxiety disorders and point toward new targets for treatment.

“We want to conceptualize psychiatric disease as real physical entities with physical substrates,” says Deisseroth. “Just like people who have asthma have reactive airways, people with anxiety disorders may have an underactive projection in the amygdala.”…Original Article »

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