ABSTRACT
Incorporating diverse molecular and cellular signaling processes into integrated, organismic-scale models of brain function is a formidable challenge for modern neuroscience. Molecular functional magnetic resonance imaging (fMRI) is a new technology that can bridge the molecular and cellular precision with whole-brain coverage in intact living animals. Here I will present two molecular fMRI techniques I have developed with my colleagues and the application of the methods to decipher the midbrain reward system. In the first part of the talk, I will discuss wide-field mapping of dopaminergic function in the striatum using molecular fMRI. By combining dopamine imaging with conventional fMRI, we can discern the topography of dopamine release and its neuromodulatory effects on postsynaptic signaling during rewarding stimulation. In addition to local effects on the magnitude and duration of neural activity, striatal dopamine potentiates a network of distal responses we can delineate using neurochemically-dependent functional connectivity analysis. In the second part of the talk, I will introduce “hemogenetic fMRI,” which ties intracellular calcium signaling of genetically targeted cells/circuits to fMRI readouts. Essentially, it is a noninvasive MRI analog of optical imaging with GCaMP. I will discuss validation of the tool and its initial application for characterizing a brain-wide network of monosynaptic inputs to the striatum activated in a reward paradigm in rats. The results reveal engagement of diverse projection sources. Pathways of information flow are distinct from those suggested by standard correlational or anatomical connectivity measures. This is the first time that fMRI signals can provide neural circuit specificity. This emerging technique offers an unprecedented avenue to map the activity of genetically-targeted cells/circuits, providing input-output analysis of brain-wide neural circuits in living rodents and non-human primates.
BIOGRAPHY
Dr. Li is a Research Associate from Alan Jasanoff Lab in the Department of Biological Engineering at the Massachusetts Institute of Technology. Her general research interest is to develop and implement novel neuroimaging techniques to solve brain science problems by integrating molecular and system neuroscience, in health and disease. Dr. Li received her B.S. from Shanghai Jiao Tong University in China, and her Ph.D. from Johns Hopkins School of Medicine, both in Biomedical Engineering.
