Brain Cells Behind Overeating

Scientists have defined neurons responsible for excessive food consumption at an unprecedented level of detail.

Two independent research teams have defined populations of neurons in the hypothalamus that are responsible for food-as-reward stimulation, but are likely not necessary to spur eating for survival. Both groups published their findings today (January 29) in Cell.

“These are big papers that start to define the complexity and heterogeneity of [the hypothalamus] and the specific sets of neurons that can produce dramatic behavioral results,” saidRalph DiLeone, a neurobiologist at Yale University who was not involved in the work.

Using optogenetics, neuroscientist Garret Stuber at the University of North Carolina, Chapel Hill, and his colleagues found that activating GABAergic neurons within the lateral hypothalamus (LH) led mice to feed more frequently, while inhibiting the activity of these neurons motivated the mice to not eat in excess. These neurons were distinct from other neuronal populations in the LH previously implicated in eating and other reward-related behaviors. When these neurons were genetically ablated, the mice were less motivated to obtain a liquid calorie reward. The scientists also visualized calcium signaling of hundreds of individual GABAergic neurons at once in free-moving mice by implanting microendoscopes into the LH and attaching a miniaturized fluorescence microscope to the animals’ heads. The calcium imaging showed distinct populations of GABAergic neurons active upon the first taste of a food reward or when the mice poked their noses—a sign of interest in the food—but rarely during both activities. Original Article »

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Sugar On The Brain Circuit: Mice Seeking Sweets May Hold Key To Compulsive Overeating

You know the feeling: you’re tired, cranky, low or just have a serious, relentless desire for something sweet. Part of your brain cries out, “No, don’t do it, this will end badly.” But another (louder) part wants what it wants and won’t let up until that pint of Cherry Garcia, or red velvet cupcake or Caramel Macchiato is in plain sight. It’s an itch that must be scratched.

Now, brain scientists at MIT say they’ve identified a specific neural circuit in mice that can increase that compulsive overeating of sweets, but doesn’t interfere with normal eating patterns necessary for survival. More specifically, turning on this set of neurons drove mice to seek the reward of a sugary drink even in the face of punishment (a shock to the foot); and compelled them to eat voraciously even when full.  When the researchers shut down this pathway, however, the compulsive sucrose-seeking decreased. Original Article »

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Decoding sugar addiction

Separate neural circuits control sugar cravings and healthy eating, researchers find.

Together, obesity and Type 2 diabetes rank among our nation’s greatest health problem, and they largely result from what many call an “addiction” to sugar. But solving this problem is more complicated than solving drug addiction, because it requires reducing the drive to eat unhealthy foods without affecting the desire to eat healthy foods when hungry.

In a new paper in Cell, neuroscientists at MIT have untangled these two processes in mice and shown that inhibiting a previously unknown brain circuit that regulates compulsive sugar consumption does not interfere with healthy eating.

“For the first time, we have identified how the brain encodes compulsive sugar seeking and we’ve also shown that it appears to be distinct from normal, adaptive eating,” says senior author Kay Tye, a principal investigator at the Picower Institute for Learning and Memory who previously developed novel techniques for studying brain circuitry in addiction and anxiety. “We need to study this circuit in more depth, but our ultimate goal is to develop safe, noninvasive approaches to avert maladaptive eating behaviors, first in mice and eventually in people.” Original Article »

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Kay Tye named 2014 NYSCF – Robertson Investigator

The Picower Institute congratulates Kay Tye, a Picower principal investigator and the Whitehead Career Development Assistant Professor in the MIT Department of Brain and Cognitive Sciences who is one of six promising scientists the New York Stem Cell Foundation (NYSCF) recently selected to receive a $1.5 million award over the next five years. The NYSCF Investigator Program, designed to support emerging scientists engaged in innovative neuroscience and stem cell research, fosters the careers of talented researchers as they transition from completing their postdoctoral studies to managing their own labs.

The Tye lab focuses on understanding how the brain processes valence: selecting the appropriate behavioral responses to positive and negative stimuli. Picower Institute researchers strive to discover specifically how emotional and motivational states, such as seeking pleasure and avoiding pain, influence learning and behavior. As one of three scientists awarded an NYSCF – Robertson Neuroscience Investigator award, Tye’s work is expected to contribute to groundbreaking discoveries in medical research.

MIT’s Feng Zhang, the W.M. Keck Career Development Professor of Biomedical Engineering and a member of the McGovern Institute for Brain Research at MIT and the Broad Institute of MIT and Harvard, was another of the six scientists receiving a 2014 NYSCF Roberston Investigators grant; he received one of three NYSCF – Robertson Stem Cell Investigator awards. Zhang is developing disruptive technologies to better understand nervous system function and disease… Original Article »

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EmTech: Meet the Innovators Under 35 – Group 4

Identifying how the connections between regions of the brain contribute to anxiety.

Kay Tye began her education as an undergraduate research assistant at MIT from 1999-2003. She continued her studies at the University of California, San Francisco as a graduate student in Patricia Janak’s lab studying electrophysiological properties of amygdala neurons both in vivo and ex vivo during reward-seeking behavior. Kay then did a short postdoc with Antonello Bonci, now the intramural director of NIDA, to study synaptic strength following reward learning, followed by a postdoc at Stanford University with Karl Deisseroth where she used novel optogenetic techniques to dissect the neural circuitry underlying psychiatric disease… Original Article »

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Nine MIT researchers win Sloan Research Fellowships

MIT researchers specializing in neuroscience, chemistry, mathematics, and ocean sciences are among 126 selected.

Three neuroscientists, three chemists, two mathematicians, and an ocean scientist from MIT are among the 126 American and Canadian researchers awarded 2014 Sloan Research Fellowships, the Alfred P. Sloan Foundation announced today.

New MIT-affiliated Sloan Research Fellows are: Gloria B. Choi, an assistant professor of brain and cognitive sciences; Mircea Dinca, an assistant professor of chemistry; Mehrdad Jazayeri, an assistant professor of brain and cognitive sciences; Jeremiah A. Johnson, an assistant professor of chemistry; Kristopher Karnauskas, an associate researcher at the Woods Hole Oceanographic Institution; Bradley Olsen, an assistant professor of chemical engineering; Charles Smart, an assistant professor of mathematics; Jared Speck, an assistant professor of mathematics; and Kay Tye, an assistant professor of brain and cognitive sciences.

Awarded annually since 1955, Sloan Research Fellowships are given to early-career scientists and scholars whose achievements and potential identify them as rising stars among the next generation of scientific leaders. This year’s recipients are drawn from 61 colleges and universities across the United States and Canada… Original Article »

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Kay Tye Named to Tech Review’s Top-Innovators List

Today, MIT Technology Review revealed its annual list of Innovators Under 35. For more than a decade, the publication has recognized a list of exceptionally talented technologists whose work has great potential to transform the world.

For her work in biotechnology and medicine, Kay Tye, an assistant professor of brain and cognitive sciences and a member of the Picower Institute for Learning and Memory, has earned a spot on that list.

Tye pioneered the manipulation of specific projections in the brain. Specifically, she was the first to publish the demonstration, characterization, and application of both excitation and inhibition of specific neural pathways, or populations of synapses. Her work is said to have revolutionized the field of neuroscience by establishing causal relationships between specific populations of synapses and behavior.

“Over the years, we’ve had success in choosing young innovators whose work has been profoundly influential on the direction of human affairs,” the Technology Review’s editor-in-chief and publisher Jason Pontin said. “Previous winners include Larry Page and Sergey Brin, the cofounders of Google; Mark Zuckerberg, the cofounder of Facebook; Jonathan Ive, the chief designer of Apple; and David Karp, the creator of Tumblr. We’re proud of our selections and the variety of achievements they celebrate, and we’re proud to add Kay Tye to this prestigious list.”… Original Article »

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Distinct Amygdala Projections Control Opposing Behavioral Outputs

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 have 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… Original Article »

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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… Original Article »

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Why map brains?

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.’… Original Article »

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A Common Brain Pathway for Anxiety and Social Behavior

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 of 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… Original Article »

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Creative Minds: Trying to Curb Those 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… Original Article »

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

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 have 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 »

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