Alan Jasanoff

Associate Professor of Biological Engineering with appointments in Brain and Cognitive Sciences and Nuclear Science and Engineering, MIT Neuroscience
Associate member of the McGovern Institute
Principal Investigator, Jasanoff Lab

Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the human brain, but the method is now approaching the limit of its capabilities. Alan Jasanoff hopes to break through this limit and to develop new technologies for imaging the molecular and cellular phenomena that underlie brain function.

Web Information

McGovern Webpage: mcgovern.mit.edu/principal-investigators/alan-jasanoff

Lab page:  mit.edu/~jasanofflab/

Department of Brain and Cognitive Sciences page: bcs.mit.edu/people/jasanoff.html

MIT Neuroscience: neuroscience.onair.cc/mit-neuroscience/

Contact Information

Email: jasanoff@mit.edu

Phone:617-452-2538 

Address: MIT Rm. 16-561 | 77 Massachusetts Avenue | Cambridge, MA 02139

Alan Jasanoff

Alan Jasanoff

Biography

Alan Jasanoff is an associate member of the McGovern Institute and Associate Professor of Biological Engineering, with appointments in Brain and Cognitive Sciences and Nuclear Science and Engineering.  He was awarded tenure in 2011. Prior to joining the MIT faculty, he was a Whitehead Fellow at the Whitehead Institute for Biomedical Research at MIT. He was named a Raymond and Beverly Sackler Foundation Scholar in 2004 and received the McKnight Technological Innovations in Neuroscience Award in 2006. Jasanoff was also a 2007 recipient of the Director’s New Innovator Award from the National Institutes of Health.

Research

From website:

Pushing the frontiers of MRI

Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the human brain, but the method is now approaching the limit of its capabilities. Alan Jasanoff hopes to break through this limit and to develop new technologies for imaging the molecular and cellular phenomena that underlie brain function.

Beyond blood flow

Functional MRI takes advantage of the fact that when a particular brain region becomes more active it consumes more oxygen, and blood flow increases to that region increases to compensate. These changes can be detected during a brain scan because the blood protein hemoglobin changes its magnetic properties when it is depleted of oxygen.

Although fMRI has yielded much valuable information, it suffers from two fundamental limitations. First, changes in the blood are slow relative to the speed of neural activity, making it impossible to measure rapid brain events. Second, the source of the activity can only be localized to the nearest blood vessel. It is not precise enough to provide detailed information about activity in specific neurons and circuits.

Jasanoff is working to overcome these limitations. He is devising new contrast agents whose magnetic properties are altered by events in the neurons themselves, rather than their surrounding blood vessels. If successful, such an approach could reveal an unprecedented level of information about brain activity as it unfolds in real time.

The next generation of contrast agents

When neurons become active, they rapidly take up calcium from their environment. Jasanoff hopes to visualize these rapid changes using magnetic nanoparticles that are coupled to a calcium-binding protein. In collaboration with colleagues at the MIT chemistry department, he is also developing a new class of molecules that can be engineered to accumulate inside cells and to reveal changes in the intracellular chemical environment.

Another one of Jasanoff’s approaches is to develop indicator molecules that can be genetically encoded and targeted to specific cell types. Jasanoff is developing an indicator for dopamine. Dopamine is a neurotransmitter that is depleted in Parkinson’s disease. Many psychiatric drugs and substances of abuse target dopamine receptors in the brain. So the ability to detect changes in dopamine in living animals would have many applications for the study of brain disorders. Eventually, Jasanoff hopes it may be possible to adapt the approach for use in human subjects, thereby providing a powerful new tool for clinical research and drug development.

Lab

Publications

Presentations

Alan Jasanoff: Molecular Probes for Noninvasive Neuroimaging

Tech Day 2013: Alan Jasanoff – Dissecting the Brain

Articles

Delving deep into the brain

MIT News 5/1/14 by Anne Trafton

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 ofScience, 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.

 

Skip to toolbar