Homeostatic circuits selectively gate food cue responses in insular cortex

Area of Science:

• Neuroscience
• Physiology
• Behavioral Science

Background:

• Physiological needs, such as hunger, influence perception and attention.
• Dysregulation of these processes is linked to addiction, obesity, and eating disorders.
• The insular cortex is implicated in processing motivationally relevant cues, but the underlying circuit mechanisms are unclear.

Purpose of the Study:

• To investigate how subcortical circuits bias cortical processing of motivationally relevant cues based on physiological states.
• To elucidate the neural pathways involved in hunger-driven modulation of insular cortex activity.

Main Methods:

• Developed a microprism-based cellular imaging technique to monitor insular cortex neuronal activity in behaving mice.
• Manipulated hypothalamic Agouti-related peptide (AgRP) neurons using chemogenetics.
• Mapped neural pathways using circuit tracing and pathway-specific manipulations.

Main Results:

• Insular cortex neurons exhibited food-cue-biased responses that were diminished during satiety.
• Chemogenetic activation of AgRP 'hunger neurons' restored hunger-like insular cortex responses, independent of visceral satiety signals.
• Identified a novel pathway from AgRP neurons to the insular cortex via the paraventricular thalamus and basolateral amygdala.

Conclusions:

• Revealed a neural circuit basis for how physiological states, specifically hunger, bias sensory cue processing in the insular cortex.
• Demonstrated that hypothalamic hunger signals can directly modulate insular cortex activity, overriding satiety cues.
• This finding has implications for understanding motivated behaviors and disorders like addiction and obesity.