Our laboratory studies how sensory stimuli drive behavioral responses and internal states depending on past experience. We focus at the level of neural circuits, using olfaction as a model to address xthree central problems.
Both environmental and genetic factors contribute to the development of neurological disorders characterized by both abnormal behavioral outcomes and brain pathologies. One environmental factor that has been studied extensively is Maternal Immune Activation (MIA), which exposes a developing fetus to inflammation. In mouse models of maternal inflammation, behavioral abnormalities are observed in adult mice whose mothers were exposed to either viral infection or a synthetic dsRNA (poly(I:C)) mimicking viral infection. Using both genetic mutants and blocking antibodies targeting their activities, we recently found that Th17 cells are critical mediators working in pregnant mice to induce the behavioral abnormalities in MIA-affected offspring. T cell-specific inactivation of RORγt in mothers (which selectively removes Th17 cells in pregnant mothers) prevented MIA-dependent behavioral phenotypes in offspring. In addition, we found that maternal inflammation leads to abnormal cortical phenotypes in offspring and that this malformation is fully rescued by inhibiting the maternal IL-17a pathway. We also established that the receptor for IL-17 (IL-17R) is expressed in the developing fetal brain, and its expression is increased in the cortex upon MIA. Building on these findings, we are now asking if uncontrolled activation of IL-17R expressed in fetal brain induces abnormal cortical development and whether these structural abnormalities are the underlying cause of the MIA-dependent behavioral phenotypes. In the process, we plan to identify the neural circuits affected by MIA, with the goal of modulating the neuronal activities of these circuits as therapeutic approaches to ameliorating MIA-induced behavioral phenotypes. More broadly, we are taking a multi-disciplinary approach—including traditional and CRISPR-based genome editing, molecular, optogenetic, in vivo and ex vivo electrophysiological, and various imaging techniques—to understand how the immune system influences the brain and modulates neural circuits to shape and guide behavioral outputs.
Learning plays a broad role shaping behavior in animals with imposed social structures. We humans attach personal meaning to the simple smell of coffee, or a perfume, or the aroma of...Read more
Animals adapt to ever-changing environments by rapidly modifying their behavior to accommodate the evolving rules and contingencies of their current situations...Read more
Olfactory perception begins with the recognition of odorants by a large repertoire of olfactory receptors (OR) in the sensory epithelium. In the mouse, each sensory neuron...Read more