In search of smell's meaning
Gloria Choi's research addresses the mechanisms by which the brain learns to recognize olfactory stimuli and to associate them with appropriate behavioral responses.
Much recent work has been devoted to the question of how the binding of odorant molecules to their receptors in the olfactory epithelium leads to the perception of odors. In other sensory modalities such as vision, touch or hearing, the primary sensory cortex shows a topographical organization in which stimulus features are systematically mapped on the cortical surface. In the olfactory area (known as piriform cortex), however, no such order has been found; while individual inputs to the cortex are tuned to specific odorants, their projections within the piriform cortex are widely dispersed. Consistent with this, olfactory stimuli typically activate sparse ensembles of piriform cells, with no obvious spatial pattern. Yet somehow the brain must learn to recognize these apparently arbitrary spatial patterns of activity and to endow them with behavioral significance.
Choi uses the power of rodent molecular genetics to study how this happens. Using the optogenetic molecule Channelrhodopsin2, she has been able to activate sparse arbitrarily-chosen populations of neurons within the piriform cortex using direct light stimulation. She has shown that animals can learn to recognize and distinguish these artificial ‘smell-like’ cues, which can be flexibly associated with either rewarding or aversive stimuli to drive the appropriate behavioral responses.
A prominent example of this type of behavior is the formation of social memories based on olfactory cues. Mice readily learn to associate odors with socially significant cues such as a prospective mate or an aggressive or threatening individual. In her lab at MIT, Choi has shown that the hormone oxytocin plays an important role in forming these social associations, by acting on cells within the piriform cortex.
Maternal infection and psychiatric disorders
In another line of work, Choi studies the effect of maternal inflammation on prenatal brain development. Epidemiological studies in human populations have indicated that infections during pregnancy are associated with increased risk of disorders such as schizophrenia and autism. By modeling this effect in mice, Choi has found that maternal inflammation leads to abnormalities of brain structure and social behavior in the offspring. These effects are triggered by an immune signaling molecule known as IL-17a, implying that targeting this signaling pathway in susceptible pregnant mothers might reduce the risk of inflammation-associated psychiatric disorders.
Gloria Choi joined the MIT faculty in 2013 as a McGovern Investigator and an assistant professor in the Department of Brain and Cognitive Sciences, where she holds the Samuel A. Goldblith Career Development Professorship. Choi received her Ph.D. from Caltech, where she studied with David Anderson, following which she conducted post-doctoral research in the laboratory of Richard Axel at Columbia University. In 2014 she was named to Cell’s ‘40 under 40’ list.