Insular cortex selective processing of need-relevant cues via distinct hypothalamic circuits

Physiological needs bias perception and attention to relevant sensory. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Human neuroimaging studies implicate insular cortex (InsCtx) in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally-relevant cues are biased by subcortical circuits driving specific motivational states. We approached this question by focusing on both ends of the problem, and how they interact: InsCtx on one end, and hypothalamic neurons driving specific need states on the other end. 

We developed a microprism-based cellular imaging approach to monitor InsCtx activity in behaving mice across different physiological states. We examined InsCtx cue responses during hunger/satiety states, and thirst/quenched states. We found that cortical response patterns during natural need states could be mimicked by chemogenetic activation of hypothalamic “hunger neurons” or “thirst neurons”.  Circuit-mapping and pathway-specific manipulations uncovered a convergent pathway that links these hypothalamic neurons to InsCtx, via paraventricular thalamus (PVT) and basolateral amygdala (BLA). 

Finally, we found that InsCtx ongoing activity, rather than task-related activity, represents physiological state (thirsty/quenched/hungry/sated). Ongoing activity could predict subsequent changes in behavior long before they occur. Furthermore, while activation of hypothalamic “thirst neurons” restored cue-evoked activity; it did not restore ongoing activity to a thirst-like state. This supports a model in which InsCtx integrates limbic inputs, which are modulated by hypothalamic need-driving neurons, with feed-forward visceral inputs from thalamus and brainstem, to compute an interoceptive prediction of future state. 


I did my PhD at The Hebrew University of Jerusalem, Israel with Dr. Adi Mizrahi. In my graduate research, I combined molecular tools, with in vivo time-lapse two-photon imaging, and two-photon-targeted electrophysiology to explore the development and plasticity of adult-born neurons. I am currently a postdoc with Dr. Mark Andermann and Dr. Brad Lowell at BIDMC and Harvard Medical School, investigating how the physiological state of the body affects perception and attention to need-relevant cues in the environment. I am focusing on insular cortex as a central hub that integrates autonomic and limbic information to guide behavior. 

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