Brainmap: DREAMM: Whole-brain molecular dissection of cell type-specific circuits in freely-moving animals as a tool for studying normal behavior and psychiatric disease

Wednesday, October 22, 2014 - 12:00
Seminar room 2204, Bldg. 149, Charlestown Navy Yard

Michael Michaelides,  Ph.D.
Postdoctoral Fellow, Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai
 
The mammalian brain is a complex organ with billions of heterogeneous cells whose local and long-range functional connections regulate behavior and physiology. Traditional in vivo approaches for mapping functional brain anatomy and molecular changes are largely invasive, non-molecular, and implemented on anesthetized or immobilized animals. To overcome these limitations, we developed imaging methodologies that enable non-invasive, dynamic, quantitative, high-resolution, molecular, whole-brain assessments of cell type-specific functional anatomy in freely-moving animals. We have used these to map discrete behavioral profiles to whole-brain functional anatomy elicited in response to transient manipulation of direct and indirect pathways of the nucleus accumbens shell in rats (Michaelides et al 2013, J Clin Invest). We have also coupled these imaging techniques to stress- and anxiety-related behavioral, physiological, and molecular measures, elicited upon transient prodynorphin neuron manipulations in a discrete amygdala nucleus in rats, in concert with relevant measures in humans, to identify translational circuits relevant to substance abuse and depression (Anderson et al 2013, J Clin Invest). More recently, we have extended the use of these imaging methodologies to mice, where we mapped anxiety- and depression-related behaviors to concurrent engagement of whole-brain functional anatomy driven by manipulations of serotonin dorsal raphe neurons. Finally, we have used these techniques to identify a novel metabolic-reward brain circuit interface, integrating appetitive drive, reward learning, and metabolism, and its relevance to obesity. Overall, these approaches fill a technological niche providing unbiased, direct, quantitative, molecular, and longitudinal information on whole-brain functional anatomy and molecular neurobiology and thus can be used as an important reverse-engineering research strategy to dissect cell type- and in vivo-specific neuronal networks associated with normal as well as pathologic behavior.