Two parabrachial Cck neurons involved in the feedback control of thirst or salt appetite

Thirst and salt appetite are temporarily suppressed after water and salt ingestion, respectively, before absorption; however, the underlying neural mechanisms remain unclear. The parabrachial nucleus (PBN) is the relay center of ingestion signals from the digestive organs. We herein identify two distinct neuronal populations expressing cholecystokinin (Cck) mRNA in the lateral PBN that are activated in response to water and salt intake, respectively. The two Cck neurons in the dorsal-lateral compartment of the PBN project to the median preoptic nucleus and ventral part of the bed nucleus of the stria terminalis, respectively. The optogenetic stimulation of respective Cck neurons suppresses thirst or salt appetite under water- or salt-depleted conditions. The combination of optogenetics and in vivo Ca²⁺ imaging during ingestion reveals that both Cck neurons control GABAergic neurons in their target nuclei. These findings provide the feedback mechanisms for the suppression of thirst and salt appetite after ingestion.