Stern Lab

Behavior is driven not only by sensing, learning, and remembering stimuli in the environment but also by integrating that learned information with internal states. In the Stern Lab, we use a wide variety of state-of-the-art techniques, including transcriptomics, chemo/optogenetics, viral tracing, in vivo calcium imaging, and computational modeling, to understand the neural mechanisms underlying this integrative function of the brain.

The process of sensing the outside environment (mediated by our five senses: visual, tactile, olfactory, gustatory, and auditory) are known as exteroception, whereas the process of sensing our internal states (hunger, body temperature, heart rate, or stress for example) is referred to as interoception. Interoceptive information is carried to the brain mainly through the vagus nerve and spinal cord to the brainstem, but also through hormones and peptides, such as leptin, insulin, and ghrelin, and neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis. This information is hypothesized to ultimately be transmitted to an understudied area of the brain, the insular cortex. Yet, how interoceptive information is encoded in the insula is almost entirely unknown.

Previous studies suggest that the insular cortex guides decision-making based on interoceptive information and that dysfunction in interoception may underlie numerous maladaptive behaviors as well as psychiatric disorders. In our lab, we primarily use feeding behavior as a model to study this process. Feeding is ideally homeostatic and innate – organisms should eat when hungry and stop when they are sated. However, obesity and eating disorders are prevalent in the developed world and are not typically caused by monogenetic disorders but rather by a combination of genetic and environmental factors. Recently, we showed that the insular cortex is required for a conditioned overconsumption task, an associative learning task in which mice overeat in response to food-associated cues, but not for homeostatic feeding based on the animal’s energy needs. This suggests that the insular cortex integrates information about the animal’s hunger state and energy balance while also integrating that with information about the sensory properties of food and/or the environment. Current projects in our lab address both aspects of this question – first, using novel behavioral paradigms and computational modeling to address how the insular cortex encodes interoceptive information. Second, by investigating how external changes in the environment, such as cues or stress, lead to short and long-term changes in feeding and the role of the insular cortex in mediating those changes.

In order to gain the most comprehensive understanding of the mechanisms by which the insular cortex alters behaviors, we innovate in a number of areas, including transcriptomics and behavioral paradigms. Single-cell sequencing has allowed the unprecedented understanding of the transcripts expressed in the brain. However, how this gene expression relates to the neural ensembles involved in complex behaviors is not well understood. Our lab uses sophisticated gene expression profiling techniques to address this question and identify novel cell types in the brain. Secondly, our lab is invested in pioneering new behavioral paradigms. One area related to feeding which has been delayed in this regard is behaviors that address restrictive eating behaviors as seen in patients with anorexia nervosa and other eating disorders. Therefore, our lab works to model restrictive eating behaviors to investigate the underlying neural circuitry.

Addressing the function of the insular cortex in guiding ingestive behavior will ultimately help us understand how interoception is integrated with learned information about the external world in order to guide and change behavior.