RT Journal Article
SR Electronic
T1 Somatodendritic release of cholecystokinin potentiates GABAergic synapses onto ventral tegmental area dopamine cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.14.476405
DO 10.1101/2022.01.14.476405
A1 Valentina Martinez Damonte
A1 Matthew B. Pomrenze
A1 Caroline Casper
A1 Annie M. Wolfden
A1 Robert C. Malenka
A1 Julie A. Kauer
YR 2022
UL http://biorxiv.org/content/early/2022/01/17/2022.01.14.476405.abstract
AB Neuropeptides are contained in nearly every neuron in the central nervous system and can be released from somatodendritic sites as well as from nerve terminals. Cholecystokinin (CCK), among the most abundant neuropeptides in the brain, is expressed in the majority of midbrain dopamine neurons. Here we report that ventral tegmental area (VTA) dopamine neurons release CCK from somatodendritic regions, where it triggers long-term potentiation of GABAergic synapses. The somatodendritic release occurs with trains of action potentials or prolonged but modest depolarization and is dependent on synaptotagmin 7 and T-type Ca2+ channels. Depolarization-induced LTP is blocked by the CCK2R antagonist, LY225910, and mimicked by exogenously added CCK. To test the behavioral role of CCK, we infused it into the mouse VTA. Ca2+ imaging in vivo demonstrated that infused CCK reduced dopamine cell signals during fasted food consumption. Moreover, local infusion of CCK also inhibited food consumption and decreased distance traveled in an open field test. Together our experiments introduce somatodendritic neuropeptide release as a previously unknown feedback regulator of VTA dopamine cell excitability and dopamine-related behaviors.Competing Interest StatementThe authors have declared no competing interest.