CONTRIBUTION OF NEURAL CIRCUITS OF THE INSULAR CORTEX IN HIGH CALORIC DIET-INDUCED ANXIETY

Anxiety is an essential emotion for survival. However, it can become pathological when it persists without potential danger. In fact, anxiety disorders have a yearly prevalence of 18%. While the causes remain unclear, obesity is a risk factor: with 20% of obese patients develop an anxiety disorder. Interestingly, studies showed that the insular cortex (insula) is altered in both obesity and anxiety disorders.
We hypothesized that the insula contributes to high caloric diet-induced anxiety.
To assess the impact of overweight on anxiety, we subjected 8-weeks-old C57BL/6J male and female mice to high caloric diet (HCD) for 12 weeks. HCD increases anxiety-related behaviors in the elevated plus maze (EPM) and novelty-suppressed feeding test.
To define the role of insula circuits in HCD-induced anxiety, we used calcium imaging to record excitatory neurons of the anterior or posterior insula and neurons of the anterior insula projecting to the nucleus accumbens or the basolateral amygdala (insula-NAc and insula-BLA), in both SD and HCD mice.
In SD mice, the activity of anterior insula neurons was higher when mice were in open arms. Interestingly, this response was amplified in HCD mice and this activity correlated with mice anxiety levels.
To investigate the mechanisms underlying anterior insula hyperexcitability after HCD, we examined neuronal excitability ex vivo and assessed neuroinflammation. Finally, we performed chemogenetic inhibition to test the causal role of neural population which exhibit increased activity after HCD. Overall, our work supports the hypothesis of a crucial contribution of the anterior insula in HCD-induced anxiety in mice.