Distinct Amygdala Projections Control Opposing Behavioral Outputs

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Monday Night Neuroscience Seminars – Kay Tye, MIT – “Distinct Amygdala Projections Control Opposing Behavioral Outputs”

The ability to differentiate between positive and negative environmental stimuli is critical to an animal’s survival. However, the neural circuits that endow the brain with the ability to differentiate positive and negative motivationally significant stimuli have been difficult to disentangle and represent one of the most important fundamental neuroscience questions today.

The development and application of optogenetic approaches has allowed us to probe the causal relationships between activity in specific circuit elements and animal behavior relevant to psychiatric disease states such as anxiety, addiction and depression. In this seminar, Kay Tye will discuss her research on the corticolimbic circuits that mediate valence processing using a multidisciplinary approach involving optogenetic, electrophysiological, pharmacological and imaging techniques… View Original Article»

Shining Light on Madness

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Shining Light on Madness

Drugs for psychiatric illnesses aren’t very effective. But new research is offering renewed hope for better medicines.

Novartis’s research lab in Cambridge, Massachusetts, a large incubator-like piece of equipment is helping give birth to a new era of psychiatric drug discovery. Inside it, bathed in soft light, lab plates hold living human stem cells; robotic arms systematically squirt nurturing compounds into the plates. Thanks to a series of techniques perfected over the last few years in labs around the world, such stem cells—capable of developing into specialized cell types—can now be created from skin cells. When stem cells derived from people with, say, autism or schizophrenia are grown inside the incubator, Novartis researchers can nudge them to develop into functioning brain cells by precisely varying the chemicals in the cell cultures.

They’re not exactly creating schizophrenic or autistic neurons, because the cells aren’t working within the circuitry of the brain, but for drug-discovery purposes it’s the next best thing. For the first time, researchers have a way to directly examine in molecular detail what’s going wrong in the brain cells of patients with these illnesses. And, critically for the pharmaceutical company, there is now a reliable method of screening for drugs that might help. Do the neurons look different from normal ones? Is there a flaw in the way they form connections? Could drugs possibly correct the abnormalities? The answer to each of these questions is a very preliminary yes… View Original Article»

Author: David Rotman

Why map brains?

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How could we benefit from better brain maps?

‘With deep brain stimulation (DBS), you’re just poking around in the dark. Stimulating brain cells with light probes rather than electrical DBS probes would be a marked improvement. We can identify targets for more effective treatments, with fewer side effects, by using these new light-based tools to study specific elements in brain circuits.

‘However, we have to do a lot more research to see how well the brain tolerates being genetically engineered with light-reactive proteins. It’s frightening to put something in your brain when you don’t yet know what the long-term effects are.’… View Original Article»

A Common Brain Pathway for Anxiety and Social Behavior

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MIT neuroscientist Kay Tye finds a discrete brain circuit that controls social interaction, which is impaired in many brain disorders.

Impaired social interaction is a common feature in autism, schizophrenia, depression, and anxiety, and it contributes to many of the problems that people with these conditions face. That is particularly true for adolescents with autism spectrum disorder, of whom about 40 percent are also diagnosed with anxiety.

A new study from Kay Tye’s laboratory at MIT found a circuit in the brain that might explain the link between impaired social interaction and anxiety in so many disorders. The circuit connects the amygdala, well known for its role in anxiety, with the hippocampus, important for learning, memory, and emotional responses.

Recently, the Tye Lab found that a discrete circuit connecting a subregion of the amygdala (the basolateral amygdala, or BLA) with the ventral hippocampus (vHPC) controlled anxiety. Activating it increased anxiety; inhibiting it decreased anxiety. In the latest study, the lab focused on this same circuit’s ability to modulate social behavior. Both studies were led by research associate Ada Felix-Ortiz… View Original Article»

Creative Minds: Trying to Curb Those Sugar Cravings

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Creative Minds Trying to Curb hose Sugar Cravings

It’s that time of year again: holiday parties and family feasts! One of the most frequently made—and most often broken—New Year’s resolutions is to follow a sensible diet.

All goes well until you catch sight of a cupcake or smell some cookies fresh out of the oven. Sensory cues trigger cravings that crumble resolve and, before you know it, you’re on a sugar high.

Actually, from a biological perspective, it’s not a fair fight. Once desires and preferences are hard-wired in the brain, people have difficulty changing their habits. But one of 2013 recipients of the NIH Director’s New Innovator Award, Kay Tye of the Massachusetts Institute of Technology (MIT), Cambridge, MA, is up for the challenge. In a high-risk, high-reward research project, she’s trying to find ways to control food cravings by reprogramming the brain, where the behavior begins.

Tye says her interest in the human brain began when she was a freshman at MIT and met H.M.—perhaps the most iconic patient in the history of brain research. H.M. was intriguing because experimental brain surgery had left him unable to form new memories, yet the old ones remained intact—a sign that there are multiple memory systems at work in the human brain. From that point on, she knew she wanted to study neuroscience, specifically memory. She began with emotional memories, including those associated with food, images, and songs. But what intrigued her the most was how emotional memories could affect health and disease… View Original Article»

Author: Dr. Francis Collins

Dissecting neural circuits underlying behaviors relevant to psychiatric disease in animal models

Events

Kay Tye gave a talk at Harvard University: “Dissecting neural circuits underlying behaviors relevant to psychiatric disease in animal models”.

The ability to differentiate between positive and negative environmental stimuli is critical to an animal’s survival.  However, the  neural circuits that endow the brain with the ability to differentiate positive and negative motivationally significant stimuli have been difficult to disentangle and represent one of the most important fundamental neuroscience questions today. The development and application of optogenetic approaches has allowed us to probe the causal relationships between activity in specific circuit elements and animal behavior relevant to psychiatric disease states such as anxiety, addiction and depression.  In this seminar, Kay Tye will discuss her research on the corticolimbic circuits that mediate valence processing… Event Link»

Three from MIT win NIH grants

News, Press Releases

Boyden, Ting and Tye receive grants for innovative medical research.

Three MIT faculty members have been awarded National Institutes of Health (NIH) grants designed to promote innovative biomedical research.

The Institute’s recipients of these NIH grants are Edward Boyden, an associate professor of biological engineering and brain and cognitive sciences; Alice Ting, the Ellen Swallow Richards Associate Professor of Chemistry; and Kay Tye, an assistant professor of brain and cognitive sciences and member of MIT’s Picower Institute for Learning and Memory.

The NIH is awarding approximately $123 million to 78 researchers across the country through its High Risk High Reward program, supported by the NIH Common Fund, which funds innovative and risk-taking research programs. The awards are divided into three categories: the NIH Director’s Pioneer, New Innovator and Transformative Research awards.

Tye, who is receiving a New Innovator Award, plans to study the obesity epidemic from the source of the problem: the compulsive consumption of unhealthy foods, such as those high in sugar. To develop a potential therapy to prevent craving from leading to compulsive behavior, she plans to use calcium imaging and electrophysiological recording data to identify the neural signature of craving. Once this neural signature of a craving state is identified, she plans to prevent the switch from craving to compulsion by transiently inhibiting the critical circuit elements using optogenetic manipulations. This research could lead to the identification of novel targets and new paradigms for obesity treatment that involve noninvasive strategies for neural manipulation such as focal ultrasound or transcranial magnetic stimulation… View Original Article»

With NIH grant, Kay Tye will take on obesity

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The MIT professor has earned a 2013 NIH Director’s New Innovator Award to further her obesity research.

MIT assistant professor of neuroscience Kay M. Tye has studied the brain circuits underlying addiction, anxiety and depression — major problems to the health of individuals and society. Now she wants to apply her training, and her own innovative techniques, to obesity research.

“Obesity is linked to the neural circuitry of the other behaviors but it may be the most pressing problem because it is the most prevalent and it is increasing,” Tye says. “Our currently available treatments for obesity are ineffective and completely insufficient for the problem that faces our society.”

So Tye proposed a strategy to discover the neural circuits underlying obesity and then reprogram them to eliminate obsessive craving and consumption. The proposal was bold, creative and risky — but it was just the kind of high-stakes project the National Institutes of Health (NIH) seeks to support with its Director’s New Innovator Award.

Now, Tye has been named a recipient of the NIH Director’s New Innovator Award for 2013 and will receive $1.5 million over the course of five years to work on her novel approach to obesity research… View Original Article»

Author: David Vaughn

Brain circuit can tune anxiety

Press Releases

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… View Original Article»

Author: Anne Trafton

From the frontline: 30 something science

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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… View Original Article»

Authors:  Heidi Ledford,  Anna Petherick,  Alison Abbott,  and Linda Nordling

Depression Eraser

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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… View Original Article»

Author: Anne Trafton

Looking at a Bright Future: Optogenetics in your Lab

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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 offer 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).

For in vivo use, an optical fiber is implanted into the brain for either acute or chronic use.  Once the light is turned on, the cells expressing ChR-2 will be activated as the channel depolarizes the cell.  Alternately, halorhodopsin expression is used to hyperpolarize a cell upon illumination, thus inactivating it at will (Tye and Deisseroth, 2012).  In many cases, this will shorten the time frame required for behavioral experiments, as intervention with optogenetics requires no “wash-out” period, as pharmacological manipulations would (Tye and Deisseroth, 2012)… View Original Article»

Dissecting the Neural Circuits Mediating Anxiety

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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 more complete view of how amygdala interactions with the rest of the brain can govern anxiety-related behaviors… View Original Video»

Video Source: Kavli Frontiers of Science