A tale of two circuits: CCKNTS neuron stimulation controls appetite and induces opposing motivational states by projections to distinct brain regions

摘要

Cholecystokinin (CCK)-expressing neurons within the nucleus of the solitary tract (CCK^NTS) are responsive to satiety signals and their chemogenetic activation suppresses appetite. Optogenetic activation of CCK^NTS axon terminals within either the parabrachial nucleus (PBN) or the paraventricular nucleus of the hypothalamus (PVH) is sufficient to suppress feeding. An interesting dichotomy has been revealed when assessing the motivational valence of these two circuits. Activating CCK^NTS cell bodies is aversive as demonstrated by conditioned taste aversion and place-preference assays. Activation of the CCK^NTS→PBN pathway is also aversive; however, stimulating the CCK^NTS→PVH pathway is appetitive when assayed using a real-time, place-preference task. Thus, these two projections from CCK^NTS neurons reduce food intake through opposite motivational states; one pathway signals positive valence (CCK^NTS→PVH) and the other signals negative valence (CCK^NTS→PBN).