Magnetic Resonance Molecular Imaging Studies of Dopaminergic Neurotransmission

Alan P. Jasanoff, Ph.D.

Massachusetts Institute of Technology

Funded in June, 2007: $200000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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MRI Imaging Sensor of Dopamine Signaling May Shed Light on Cognitive Problems in Parkinson’s

Researchers will develop an MRI imaging sensor to measure real-time signaling by the neurotransmitter dopamine, which is diminished in Parkinson’s disease, as laboratory animals undergo reinforcement (reward) learning.

Dopamine signaling pathways in the brain are involved in cognition and motor control.  Their disturbance, as occurs in Parkinson’s disease patients, for instance, results in progressively severe cognitive and movement problems. Yet scientists know little about how dopamine disruption produces damage, in large part because current experimental techniques have limited capacity to reveal the temporal and spatial patterns of dopamine release and uptake by neurons in the brain. This lack of understanding impairs efforts to try to therapeutically influence dopamine signaling for maximum benefit in patients.  The MIT researchers, therefore, will attempt to develop a high-resolution MRI imaging sensor with sufficient resolution to characterize the spatial and temporal patterns of dopamine signaling within neural networks, in real time, to provide insight into how the time-courses of local dopamine concentrations influence brain cell processing in normal and disease states.

Significance: This MRI imaging sensor could be used to gain a better understanding of how dopamine functions normally and how it malfunctions in animal models of Parkinson’s disease and addiction. It may eventually be used to provide the earliest diagnosis of Parkinson’s disease in humans and the to study effects of experimental treatments to restore effective dopamine transmission.    

ABSTRACT

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Magnetic Resonance Molecular Imaging Studies of Dopaminergic Neurotransmission

DA signaling pathways in the brain are essential for reinforcement learning and motor control and are disrupted in pathological conditions such as Parkinson’s disease and drug addiction.  Much research has focused on defining relationships between the experience of rewarding sensations and the release of DA by neurons in the dopaminergic midbrain, but far less is known about how DA affects postsynaptic structures during behavior and how time courses of local DA concentrations influence neural processing.  By characterizing spatiotemporal patterns of DA release in the brain, new molecular imaging strategies could provide critical information about both normal and pathological physiology. 

Here we therefore propose to develop a DA sensor for magnetic resonance imaging (MRI), which will for the first time allow high resolution (100 µm) functional imaging measurements of DA signaling in intact, living brains with temporal resolution on a behaviorally-relevant time scale.  Using the sensor and methods we have established for functional imaging in awake, behaving rats, we will study spatiotemporal specificity of DA signaling in an operant conditioning task and address the hypothesis that spatial patterns of DA release encode multiple, differentiated components of neural information processing during reward-related behavioral tasks.

INVESTIGATOR BIOGRAPHIES

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Alan P. Jasanoff, Ph.D.

Alan Jasanoff is the Norman Rasmussen Career Development Assistant Professor of Nuclear Science & Engineering at the Massachusetts Institute of Technology.  He graduated from Harvard College in 1992, received a masters degree in chemistry from Cambridge University in 1993, and completed a Ph.D. in biophysics at Harvard University in 1998.  From 1999 to 2004,+ he was a Whitehead Fellow at the Whitehead Institute for Biomedical Research at MIT.  Jasanoff’s laboratory is developing a new generation of brain scanning methods that will combine the specificity of cellular neuroscience with the noninvasiveness and whole-brain coverage of functional magnetic resonance imaging (fMRI).  The group focuses on creating MRI contrast agents that sense molecules important for communication between and within neurons.  The laboratory’s overall goal is to apply the new agents for high-resolution analysis of the neural mechanisms of behavior in animals.