NPP Seminar: Professor Debra Ann Fadool, Florida State University

Academic Host: Paola Pedarzani

Abstract: Our laboratory has discovered that the olfactory system plays a regulatory role in modulating energy homeostasis, and that conversely, over-nutrition can dysregulate olfactory function and correlate circuitry.  We have used CRISPR genome editing,  nanoparticle-associated drug delivery, and chemogenetics in select mouse models as strategies to modify the excitability of output neurons from the olfactory bulb.  By exciting or suppressing functional connections of the olfactory bulb to higher cortical regions, it is evident that modulation of olfaction drives changes in body weight, glucose clearance, serum chemistry, energy expenditure, adipose deposition, fuel utilization, oxygen consumption, and caloric intake.  Using mice models with reporters for olfactory circuits, we can visualize the deleterious effects of diet-induced obesity (DIO).  We can measure losses in synaptic connections in response to DIO that are associated with reduced olfactory discrimination and that fail to recover despite “dieting the mice” to normal body weight and glycemic levels.  Our lecture will discuss future approaches to uncover the mechanism of how the olfactory system communicates with central circuits to maintain metabolic health.  Use of iso-caloric feeding, voluntary running, microbiome analyses, strategic transgenic lines with modified excitable circuits, viral track tracing, gene activation, and biochemistry determinations are parallel means to determine the cellular and biophysical means by which the olfactory system contributes to balancing the body’s metabolic setpoint.  Because the olfactory system is engineered with the expression of endocrine factors, hormone receptors, and important energy signaling pathways, it is well poised to uphold a dual function to detect external chemical cues (odorants) and internal chemical cues (metabolic factors).