Neuronal circuits of interoception and emotional behavior

Glucose is the primary energy source for the brain. Its levels are constantly monitored by specialized glucose-sensing neuronal populations that have been described so far mainly in subcortical areas contributing to the regulation of energy homeostasis. Previous work of my lab examined glucose-sensing cells in the insular cortex (IC) and studied their role in emotional behavior. Monitoring c-Fos expression, a cell population activated by hypoglycemia in the mouse IC was identified. A genetic mouse model was used to target and record those cells in vitro. With this approach it was confirmed that they were glucose sensing neurons. Morphological reconstructions showed that they were thick-tufted layer 5 pyramidal cells in the posterior insula. An intersectional strategy to address those cells in vivo with chemogenetic actuators was then designed. IC glucose sensing neurons affected fear-like behavior through projection to the lateral nucleus of the central amygdala (CeL). During my master, we analyzed further the behavior to explain the heterogeneity previously observed in responses. We validated the specificity and efficiency of the chemogenetic model used. Further, we confirmed that neuronal activation in this efferent neuronal circuit was responsible of the behavior. Finally, we identified PKCδ+ neurons as downstream connections of IC glucose-sensing neurons responsible for the inhibition of fear behavior under hypoglycemia. Altogether, these data provide the first evidence of the existence of glucose-sensing neurons in the insular cortex and of a neuronal circuit linking directly interoception and emotional behavior. It brings a new understanding of the integration of internal body states for competition motivation drives