Synaptic and intrinsic plasticity mediated by CCK-type signaling coordinates behavioral changes during motivational state shifts.

Abstract

Transitions from hunger to satiety involve multiple behavioral changes, including modulation and inhibition of feeding behavior. In mammals, cholecystokinin (CCK) is a key satiety peptide implicated in these processes; however, whether and how CCK might induce satiety via synaptic and intrinsic plasticity remains unclear. Here, we investigate CCK-type signaling in the protostome mollusk Aplysia californica. We demonstrate that Aplysia CCK (apCCK) acts as a conserved brain-gut peptide. Gut-localized apCCK-expressing neurons project centrally and release apCCK near the feeding-pattern generator. In vivo, apCCK suppresses food intake, while in vitro, it shifts motor output toward egestive patterns and inhibits feeding programs. Mechanistically, apCCK modulates the excitability of the egestive-promoting B20 interneuron and suppresses synaptic input to protraction-phase motoneurons, thereby altering program selection and inhibiting feeding-program generation. These findings highlight the importance of both synaptic and intrinsic plasticity in specific circuit elements for implementing motivational shifts driven by satiety signaling.