Debra Ann Fadool

Research topics

Matched from this investigator's NIH project titles and abstracts.

• Developmental Cognitive Neuroscience
• Eating Disorders

Active NIH awards

• Probing the link between sensory systems and metabolism to prevent obesity

  5R01DK133464-03

  NIDDK · FY 2025 · $387K

  PROJECT SUMMARY The mechanism by which metabolism, diet, and olfactory function is linked is not well understood. The rising incidence of diabetes and obesity in our country is epidemic, yet little has been reported as to how chronic metabolic imbalance impacts sensory systems and whether these dysfunctions can be reversed via changes in diet, drug intervention, or selective genome editing. The work in this proposal will bridge gaps in our knowledge concerning how changes in activity of the olfactory bulb (OB) can modify energy homeostasis. To test how changes in OB excitability cause a reduction in body weight and energy metabolism, we will manipulate contribution from a voltage-dependent potassium channel, Kv1.3, exclusively in the major output neurons. Our long-term research goal is to understand how olfaction and metabolism are interrelated - to reveal how olfactory output neurons convey metabolic information. Our proposed aims are based upon the following three hypotheses: (1) Hypothesis 1 = Elimination of Kv1.3 channels in mitral/tufted cells will increase action potential firing frequency and decrease the after-hyperpolarization amplitude, selectively enhance glucose clearance, increase total energy expenditure, and decrease respiratory exchange ratio (increase fat utilization), which will produce a drop in body weight or cause a resistance to diet-induced obesity (DIO). (2) Hypothesis 2 = Odor stimulation will induce specific patterns of c-fos expression within the hypothalamus and other brain regions in mice. DIO will attenuate c-fos activation in control mice with normal Kv1.3 conduction, but not in similarly-fed, but DIO-resistant, mice in which Kv1.3 is selectively edited from mitral/tufted cells. (3) Hypothesis 3 = Restoration of Kv1.3 activity selectively in mitral/tufted cells, but not in the periphery, or decreased excitability will cause a loss in resistance to DIO as measured by body weight, glucose tolerance, and system physiology parameters. Our experiments take a multidisciplinary approach using electrophysiology, genome editing, and metabolic profiling to uncover the importance of relayed olfaction information for energy homeostasis. The knowledge generated from our proposed research defining the impact of olfactory bulb output on metabolic balance can be applied to lessen the health consequences of the rising global problem of obesity and excess food consumption. It is a high priority that we investigate coordination from extra-hypothalamic brain areas to determine their contribution to energy balance – a novel and intellectually challenging view of the olfactory system.

• Chemosensory Training Program (CTP)

  2T32DC000044-31

  NIDCD · FY 2025 · $272K

  Summary This Chemosensory Training Program (CTP), operating within the interdisciplinary Program in Neuroscience at Florida State University, is a continuing application in its 30th year. The CTP Program is geared to train the next generation of researchers to become leaders in basic neural mechanisms of chemosensory systems interfaced with behavior. The program prepares 4 pre- and 1 post-doctoral trainee for research careers focused on olfactory and gustatory senses in context. One important context is the regulation of food intake and metabolic state, dysregulation of which can lead to obesity and diabetes, or anorexia. The powerful links between chemosensory systems and brain circuitry associated with emotional, motivational, and neuromodulatory processes requires a wide perspective for full understanding. The broad long- term objective is to provide the basic neuroscience platform upon which clinical understanding of chemosensory disease is built using a wide spectrum of experimental approaches including molecular neurobiology, neurophysiology, biophysics, psychophysics, and behavioral analysis. The strength of the CTP program that anticipates to provide 2 to 3 years of training for approximately five post- and fifteen pre-doctoral scholars, respectively, is the close guidance of trainees by expert faculty whom are accustomed to productive collaborations fostered from a wealth of historical chemosensory knowledge that shapes cutting-edge investigations for training. Trainees have access to state-of-the-art custom-designed chemosensory equipment, technical support staff, and modern building infrastructure to perform their research. Value- added activities include – 1) chemosensory tutorials (hands-on lab practicum, rigor and reproducibility training), 2) “scholar in practice” (career internship with former alumni), 3) chemosensory retreat (research progress/sharing and mentor/mentee career development), 4) structured oral, written, and analysis skill building and feedback, 5) depth of a continually evolving curriculum, and 6) an opportunity for alumni and speaker interaction that relays latest discoveries, allows career networking, and provides supplementary evaluation of the training program. The CTP Training Outcomes continue to be outstanding as reflected in published productivity, trainee extramural grants, and job placement (100%-predoc and 100%- postdoc in research-intensive and -related positions). Nine expert chemosensory trainers will shape the intellectual and scientific practice of trainees at two levels as they bridge to independent and externally-funded scientific research programs in chemosensory problems important for the quality of life and human health.

• Probing the link between sensory systems and metabolism to prevent obesity

  5R01DK133464-02

  NIDDK · FY 2024 · $446K

  PROJECT SUMMARY The mechanism by which metabolism, diet, and olfactory function is linked is not well understood. The rising incidence of diabetes and obesity in our country is epidemic, yet little has been reported as to how chronic metabolic imbalance impacts sensory systems and whether these dysfunctions can be reversed via changes in diet, drug intervention, or selective genome editing. The work in this proposal will bridge gaps in our knowledge concerning how changes in activity of the olfactory bulb (OB) can modify energy homeostasis. To test how changes in OB excitability cause a reduction in body weight and energy metabolism, we will manipulate contribution from a voltage-dependent potassium channel, Kv1.3, exclusively in the major output neurons. Our long-term research goal is to understand how olfaction and metabolism are interrelated - to reveal how olfactory output neurons convey metabolic information. Our proposed aims are based upon the following three hypotheses: (1) Hypothesis 1 = Elimination of Kv1.3 channels in mitral/tufted cells will increase action potential firing frequency and decrease the after-hyperpolarization amplitude, selectively enhance glucose clearance, increase total energy expenditure, and decrease respiratory exchange ratio (increase fat utilization), which will produce a drop in body weight or cause a resistance to diet-induced obesity (DIO). (2) Hypothesis 2 = Odor stimulation will induce specific patterns of c-fos expression within the hypothalamus and other brain regions in mice. DIO will attenuate c-fos activation in control mice with normal Kv1.3 conduction, but not in similarly-fed, but DIO-resistant, mice in which Kv1.3 is selectively edited from mitral/tufted cells. (3) Hypothesis 3 = Restoration of Kv1.3 activity selectively in mitral/tufted cells, but not in the periphery, or decreased excitability will cause a loss in resistance to DIO as measured by body weight, glucose tolerance, and system physiology parameters. Our experiments take a multidisciplinary approach using electrophysiology, genome editing, and metabolic profiling to uncover the importance of relayed olfaction information for energy homeostasis. The knowledge generated from our proposed research defining the impact of olfactory bulb output on metabolic balance can be applied to lessen the health consequences of the rising global problem of obesity and excess food consumption. It is a high priority that we investigate coordination from extra-hypothalamic brain areas to determine their contribution to energy balance – a novel and intellectually challenging view of the olfactory system.

• Probing the link between sensory systems and metabolism to prevent obesity

  1R01DK133464-01A1

  NIDDK · FY 2023 · $474K

  PROJECT SUMMARY The mechanism by which metabolism, diet, and olfactory function is linked is not well understood. The rising incidence of diabetes and obesity in our country is epidemic, yet little has been reported as to how chronic metabolic imbalance impacts sensory systems and whether these dysfunctions can be reversed via changes in diet, drug intervention, or selective genome editing. The work in this proposal will bridge gaps in our knowledge concerning how changes in activity of the olfactory bulb (OB) can modify energy homeostasis. To test how changes in OB excitability cause a reduction in body weight and energy metabolism, we will manipulate contribution from a voltage-dependent potassium channel, Kv1.3, exclusively in the major output neurons. Our long-term research goal is to understand how olfaction and metabolism are interrelated - to reveal how olfactory output neurons convey metabolic information. Our proposed aims are based upon the following three hypotheses: (1) Hypothesis 1 = Elimination of Kv1.3 channels in mitral/tufted cells will increase action potential firing frequency and decrease the after-hyperpolarization amplitude, selectively enhance glucose clearance, increase total energy expenditure, and decrease respiratory exchange ratio (increase fat utilization), which will produce a drop in body weight or cause a resistance to diet-induced obesity (DIO). (2) Hypothesis 2 = Odor stimulation will induce specific patterns of c-fos expression within the hypothalamus and other brain regions in mice. DIO will attenuate c-fos activation in control mice with normal Kv1.3 conduction, but not in similarly-fed, but DIO-resistant, mice in which Kv1.3 is selectively edited from mitral/tufted cells. (3) Hypothesis 3 = Restoration of Kv1.3 activity selectively in mitral/tufted cells, but not in the periphery, or decreased excitability will cause a loss in resistance to DIO as measured by body weight, glucose tolerance, and system physiology parameters. Our experiments take a multidisciplinary approach using electrophysiology, genome editing, and metabolic profiling to uncover the importance of relayed olfaction information for energy homeostasis. The knowledge generated from our proposed research defining the impact of olfactory bulb output on metabolic balance can be applied to lessen the health consequences of the rising global problem of obesity and excess food consumption. It is a high priority that we investigate coordination from extra-hypothalamic brain areas to determine their contribution to energy balance – a novel and intellectually challenging view of the olfactory system.

Earlier awards

• Chemosensory Training ProgramFY 2024 · $214K
• Chemosensory Training ProgramFY 2023 · $278K