LAB OF NEURAL INTEROCEPTION
INTEROCEPTIVE NUTRIENT SENSING IN FLIES AND MICE
Animals in the wild encounter many types of external stimuli such as threat and food,
and must exhibit appropriate responses for survival. How does a brain recognize such
stimuli with sensory systems, create internal representations of these external stimuli,
and then elicit appropriate behavioral responses?
To address this problem, we take systems approach and use the fruit fly, Drosophila melanogaster,
because of a wealth of genetic tools available, a relatively simple brain, and a complex, interesting
behavioral repertoire. Rapidly emerging tools also permit relatively facile identification of neural
substrates. We recently launched studies using mice in addition to fruit flies. Our focus has been to identify neurons that subserve a particular innate behavior, apply functional imaging and electro-
physiology to probe their activity, therefore, define precisely contributions of each set of neurons
to behavior. We are currently interested in identification and characterization of post-ingestive,
internal sensors that detect the nutritional value of carbohydrate, fats and protein (macronutrients),
and micronutrients in Drosophila. We are extending this line of work in mice to elucidate the
identities and characteristics of the mammalian nutrient sensors, and understand the mechanisms
by which these sensors contribute to feeding and metabolism.
Among a number of discoveries that our laboratory has made thus far, we have contributed
significantly to understanding the function of Glucose-sensing neurons in the brain. Glucose-sensing
neurons were identified initially by electrophysiological recordings (Oomura et al., 1964 Science),
but the physiological function mediated by these neurons in animals were unclear until recently.
We have been able to elucidate their function using Drosophila: 1) the nutritional content of sugar,
rather than its palatability, was detected by a discrete population of glucose-excited neurons (termed
DH44 neurons) that promote sugar consumption (Dus et al., 2015 Neuron and 2011 PNAS) and
2) a pair of glucose-excited neurons (termed CN neurons) regulate the two key endocrine axes:
insulin and glucagon (Oh et al., 2019 Nature). These are a series of significant discoveries because
approximately 10-15% of neurons in our brain are glucose-sensing, but it has taken over 50 years to
reveal their physiological function in an animal. Understanding the functions of glucose-sensing in Drosophila would provide a foundation for studying their functions in mice and humans, and
developing therapeutic potentials for health issues such as obesity, diabetes, eating disorders.