Insular–brainstem circuit linked to anxiety-related behavior in mice and humans

Researchers investigated a pathway connecting CRH-expressing neurons in the anterior and middle insular cortex to the parabrachial nucleus (PBN) and posterior paraventricular thalamus. In mice, single-cell calcium imaging showed that predator odor and footshock activated partly overlapping populations of PBN-projecting insular neurons. The study also examined CRF signaling in the PBN and tested circuit inhibition, CRH knockdown, and CRF receptor 1 blockade in behavioral experiments.

Predator-odor exposure increased CRF signals in the PBN, where CRF enhanced neuronal excitability and supported firing elicited by insular inputs. Inhibiting the insula-to-PBN projection, reducing insular CRH, or blocking PBN CRFR1 attenuated odor-induced anxiety-like behavior. In a separate human neuroimaging analysis, stronger functional coupling in a putative homologous insula–PBN–thalamus network was associated with anxiety symptoms and their severity.

The findings provide a possible circuit-level account of anxiety-related states, but do not establish a treatment target or demonstrate clinical benefit. The behavioral interventions were conducted in mice, and the human results show an association rather than causation. The supplied text does not report sample sizes or enough methodological detail to assess the human analysis further.