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

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.