Disruptive Innovations in Neuroscience: Michael Lin

McGovern Institute Spring Symposium 2014
May 2, 2014
Michael Lin, Stanford University
“GFP as an optogenetic Swiss Army knife: New applications in voltage sensing, memory visualization, and optical control of protein activity”

Long range connections in the brain

This video shows white matter tracts, the long-range connections of the human brain. The tracts are revealed here through a MRI-based method known as ‘diffusion tensor imaging’ or DTI. The video is based on data produced by Dr Satrajit Ghosh at the McGovern Institute for Brain Research at MIT.

Delving deep into the brain

Launched in 2013, the national BRAIN Initiative aims to revolutionize our understanding of cognition by mapping the activity of every neuron in the human brain, revealing how brain circuits interact to create memories, learn new skills, and interpret the world around us.

Before that can happen, neuroscientists need new tools that will let them probe the brain more deeply and in greater detail, says Alan Jasanoff, an MIT associate professor of biological engineering. “There’s a general recognition that in order to understand the brain’s processes in comprehensive detail, we need ways to monitor neural function deep in the brain with spatial, temporal, and functional precision,” he says.

Jasanoff and colleagues have now taken a step toward that goal: They have established a technique that allows them to track neural communication in the brain over time, using magnetic resonance imaging (MRI) along with a specialized molecular sensor. This is the first time anyone has been able to map neural signals with high precision over large brain regions in living animals, offering a new window on brain function, says Jasanoff, who is also an associate member of MIT’s McGovern Institute for Brain Research.

His team used this molecular imaging approach, described in the May 1 online edition of Science, to study the neurotransmitter dopamine in a region called the ventral striatum, which is involved in motivation, reward, and reinforcement of behavior. In future studies, Jasanoff plans to combine dopamine imaging with functional MRI techniques that measure overall brain activity to gain a better understanding of how dopamine levels influence neural circuitry.

“We want to be able to relate dopamine signaling to other neural processes that are going on,” Jasanoff says. “We can look at different types of stimuli and try to understand what dopamine is doing in different brain regions and relate it to other measures of brain function.”

Tracking dopamine

Dopamine is one of many neurotransmitters that help neurons to communicate with each other over short distances. Much of the brain’s dopamine is produced by a structure called the ventral tegmental area (VTA). This dopamine travels through the mesolimbic pathway to the ventral striatum, where it combines with sensory information from other parts of the brain to reinforce behavior and help the brain learn new tasks and motor functions. This circuit also plays a major role in addiction.
To track dopamine’s role in neural communication, the researchers used an MRI sensor they had previously designed, consisting of an iron-containing protein that acts as a weak magnet. When the sensor binds to dopamine, its magnetic interactions with the surrounding tissue weaken, which dims the tissue’s MRI signal. This allows the researchers to see where in the brain dopamine is being released. The researchers also developed an algorithm that lets them calculate the precise amount of dopamine present in each fraction of a cubic millimeter of the ventral striatum.

After delivering the MRI sensor to the ventral striatum of rats, Jasanoff’s team electrically stimulated the mesolimbic pathway and was able to detect exactly where in the ventral striatum dopamine was released. An area known as the nucleus accumbens core, known to be one of the main targets of dopamine from the VTA, showed the highest levels. The researchers also saw that some dopamine is released in neighboring regions such as the ventral pallidum, which regulates motivation and emotions, and parts of the thalamus, which relays sensory and motor signals in the brain.

Each dopamine stimulation lasted for 16 seconds and the researchers took an MRI image every eight seconds, allowing them to track how dopamine levels changed as the neurotransmitter was released from cells and then disappeared. “We could divide up the map into different regions of interest and determine dynamics separately for each of those regions,” Jasanoff says.

He and his colleagues plan to build on this work by expanding their studies to other parts of the brain, including the areas most affected by Parkinson’s disease, which is caused by the death of dopamine-generating cells. Jasanoff’s lab is also working on sensors to track other neurotransmitters, allowing them to study interactions between neurotransmitters during different tasks.

The paper’s lead author is postdoc Taekwan Lee. Technical assistant Lili Cai and postdocs Victor Lelyveld and Aviad Hai also contributed to the research, which was funded by the National Institutes of Health and the Defense Advanced Research Projects Agency.

Feng Zhang wins NSF’s Alan T. Waterman Award

The National Science Foundation (NSF) named Feng Zhang the 2014 recipient of its Alan T. Waterman Award. This award is NSF’s highest honor that annually recognizes an outstanding researcher under the age of 35 and funds his or her research in any field of science or engineering. Zhang’s research focuses on understanding how the brain works.

“It is a great pleasure to honor Feng Zhang with this award for his young, impressive career,” said NSF Director France Córdova. “It is exciting to support his continued fundamental research, which is certain to impact the field of brain research. Imagine a future free of schizophrenia, autism and other brain disorders that wreak havoc on individuals, families and society. Feng’s research moves us in that direction.”

Zhang seeks to understand the molecular machinery of brain cells through the development and application of innovative technologies. He created and is continuing to perfect tools that afford researchers precise control over biological activities occurring inside the cell. With these tools, researchers can deepen their understanding of how the genome works, and how it influences the development and function of the brain. Zhang also examines failures within the systems that cause disease.

Two different lines of fundamental research and technology development are helping him do that: optogenetics and genome engineering. With Edward Boyden and Karl Deisseroth at Stanford University, he developed optogenetics to study brain circuits, a technique in which light is used to affect signaling and gene expression of neurons involved in complex behaviors. Zhang also developed the CRISPR system to enable new, cheaper, more effective ways to “edit” animal genomes–that is, to identify and cut a short DNA sequence underlying a disorder so that it may be deleted or substituted out for other genetic material. Although Zhang’s main area of focus is the brain, the potential applications of CRISPR technology extend well beyond neuroscience.

“This is an immensely exciting time for the field because of the tremendous potential of tools like CRISPR, which allows us to modify the genomes of mammalian cells,” Zhang said. “One of my long-term goals is to better understand the molecular mechanisms of brain function and identify new ways to treat devastating neurological disorders.”

Since high school, Zhang has devoted his time, energy and intellectual prowess to developing ways to study and repair the nervous system. Today, he is one of 11 core faculty members at the Broad Institute of MIT and Harvard; an investigator at MIT’s McGovern Institute for Brain Research; and the W. M. Keck Career Development Professor with a joint appointment in MIT’s Departments of Brain and Cognitive Sciences and Biological Engineering.

Zhang is widely recognized for his pioneering work in optogenetics and genome editing. He shared the Perl/UNC Neuroscience Prize with Karl Deisseroth and Edward Boyden in 2012. In 2013, MIT Technology Review recognized him as a “pioneer” and one of its 35 Innovators Under 35; Popular Science magazine placed Zhang on its Brilliant 10, an annual list of the most promising scientific innovators. Nature also named him as one of the “ten people who mattered” in 2013 for his work on developing the CRISPR system for genome editing in mammalian cells.

The Waterman award will be presented to Zhang at an evening ceremony at the U.S. Department of State in Washington, D.C., on May 6. At that event, the National Science Board will also present its 2014 Vannevar Bush award to mathematician Richard Tapia and Public Service awards to bioethicist Arthur Caplan and to the AAAS Science & Technology Policy Fellowships Program.

Plans are underway for Zhang to deliver a lecture at a meeting of the National Science Board at NSF and to meet with students at Thomas Jefferson High School for Science and Technology during his visit this spring.

How the brain pays attention

Picking out a face in the crowd is a complicated task: Your brain has to retrieve the memory of the face you’re seeking, then hold it in place while scanning the crowd, paying special attention to finding a match.

A new study by MIT neuroscientists reveals how the brain achieves this type of focused attention on faces or other objects: A part of the prefrontal cortex known as the inferior frontal junction (IFJ) controls visual processing areas that are tuned to recognize a specific category of objects, the researchers report in the April 10 online edition of Science.

Scientists know much less about this type of attention, known as object-based attention, than spatial attention, which involves focusing on what’s happening in a particular location. However, the new findings suggest that these two types of attention have similar mechanisms involving related brain regions, says Robert Desimone, the Doris and Don Berkey Professor of Neuroscience, director of MIT’s McGovern Institute for Brain Research, and senior author of the paper.

“The interactions are surprisingly similar to those seen in spatial attention,” Desimone says. “It seems like it’s a parallel process involving different areas.”

In both cases, the prefrontal cortex — the control center for most cognitive functions — appears to take charge of the brain’s attention and control relevant parts of the visual cortex, which receives sensory input. For spatial attention, that involves regions of the visual cortex that map to a particular area within the visual field.

In the new study, the researchers found that IFJ coordinates with a brain region that processes faces, known as the fusiform face area (FFA), and a region that interprets information about places, known as the parahippocampal place area (PPA). The FFA and PPA were first identified in the human cortex by Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience at MIT.

The IFJ has previously been implicated in a cognitive ability known as working memory, which is what allows us to gather and coordinate information while performing a task — such as remembering and dialing a phone number, or doing a math problem.

For this study, the researchers used magnetoencephalography (MEG) to scan human subjects as they viewed a series of overlapping images of faces and houses. Unlike functional magnetic resonance imaging (fMRI), which is commonly used to measure brain activity, MEG can reveal the precise timing of neural activity, down to the millisecond. The researchers presented the overlapping streams at two different rhythms — two images per second and 1.5 images per second — allowing them to identify brain regions responding to those stimuli.

“We wanted to frequency-tag each stimulus with different rhythms. When you look at all of the brain activity, you can tell apart signals that are engaged in processing each stimulus,” says Daniel Baldauf, a postdoc at the McGovern Institute and the lead author of the paper.

Each subject was told to pay attention to either faces or houses; because the houses and faces were in the same spot, the brain could not use spatial information to distinguish them. When the subjects were told to look for faces, activity in the FFA and the IFJ became synchronized, suggesting that they were communicating with each other. When the subjects paid attention to houses, the IFJ synchronized instead with the PPA.

The researchers also found that the communication was initiated by the IFJ and the activity was staggered by 20 milliseconds — about the amount of time it would take for neurons to electrically convey information from the IFJ to either the FFA or PPA. The researchers believe that the IFJ holds onto the idea of the object that the brain is looking for and directs the correct part of the brain to look for it.
Further bolstering this idea, the researchers used an MRI-based method to measure the white matter that connects different brain regions and found that the IFJ is highly connected with both the FFA and PPA.

Members of Desimone’s lab are now studying how the brain shifts its focus between different types of sensory input, such as vision and hearing. They are also investigating whether it might be possible to train people to better focus their attention by controlling the brain interactions  involved in this process.

“You have to identify the basic neural mechanisms and do basic research studies, which sometimes generate ideas for things that could be of practical benefit,” Desimone says. “It’s too early to say whether this training is even going to work at all, but it’s something that we’re actively pursuing.”

The research was funded by the National Institutes of Health and the National Science Foundation.

“Fear, Trauma, and Memory: A Panel Discussion”

How accurate are our memories after a traumatic event? Does chronic stress make us more vulnerable to trauma? Will scientists one day succeed in preventing PTSD?

We invite you to join the discussion with a distinguished group of experts who will explore new lines of research and treatment strategies for stress disorders and traumatic memory. On Monday, April 7th, McGovern Institute director Bob Desimone will moderate a panel of experts and will engage the audience in a Q&A session. This event is free and open to the public, but registration is required. We hope you will join us!

– See more at: http://mcgovern.mit.edu/news/talks-events-news/fear-trauma-and-memory-a-panel-discussion/#sthash.Z8u0CLmP.dpuf

2014 McGovern Institute Spring Symposium

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DATE: Friday May 2, 2014
TIME: 8:30am – 5:15pm
LOCATION: MIT Bldg 46-3002 (Singleton Auditorium)
QUESTIONS? Laura Dargus | ldargus@mit.edu | 617.715.5396

Registration is now closed. Selected talks from the symposium may be viewed in our video gallery.

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SYMPOSIUM SCHEDULE

 

8:30 am
Check-In

9:00 am – 9:15 am
Robert Desimone and Feng Zhang, McGovern Institute
Welcoming Remarks

Session I

Chair: Alan Jasanoff, McGovern Institute

9:15 am – 9:55 am

Alice Ting (Massachusetts Institute of Technology)
Spatially-resolved proteomic mapping of living cells using engineered peroxidase reporters

9:55 am – 10:35 am
Alex Shalek (Harvard University)
Using single cell transcriptomics to explore cellular identity and uncover drivers of cellular behaviors
watch video

10:35 am – 10:50 am
Break

10:50 am – 11:30 am
Joseph Ecker (The Salk Institute)
Global epigenomic reconfiguration during mammalian brain development

11:30 am – 12:10 pm
Je Hyuk Lee (Harvard Medical School)
Highly multiplexed subcellular RNA sequencing in situ
watch video

12:10 pm – 1:00 pm
Break

Session II

Chair: Gloria Choi, McGovern Institute

1:00 pm – 1:40 pm
Connie Cepko (Harvard University)
GFP as a regulator of biological activities
watch video

1:40 pm – 2:20 pm
Kwanghun Chung (Massachusetts Institute of Technology)
CLARITY and beyond: Towards fully-integrated multi-dimensional investigation of the brain

2:20 pm – 3:00 pm
Jeff Lichtman (Harvard University)
Connectomics
watch video

3:00 pm – 3:15 pm
Break

Session III

Chair: Ed Boyden, McGovern Institute

3:15 pm – 3:55 pm
Michael Lin (Stanford University)
GFP as an optogenetic Swiss Army knife: new applications in voltage sensing, memory visualization, and optical control of protein activity
watch video

3:55 pm – 4:35 pm
Loren Looger (HHMI, Janelia Farm)
New tools for imaging and controlling neurons in vivo

4:35 pm – 5:15 pm
Charles Lieber (Harvard University)
Nanoelectronics meets neuroscience: Novel tools for mapping to electronic therapeutics

5:15 pm – 6:15 pm
Reception in atrium

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