TY - JOUR T1 - Intrinsic regulators of the action potential waveform control dopamine release to shape behavior JF - bioRxiv DO - 10.1101/2021.08.27.457972 SP - 2021.08.27.457972 AU - Barbara Juarez AU - Mi-Seon Kong AU - Yong S. Jo AU - Jordan E. Elum AU - Joshua X. Yee AU - Scott Ng-Evans AU - Marcella Cline AU - Avery C. Hunker AU - Madison A. Baird AU - Meagan A. Quinlan AU - Adriana Mendez AU - Nastacia L. Goodwin AU - Marta E. Soden AU - Larry S. Zweifel Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/28/2021.08.27.457972.abstract N2 - Despite the widely known role of dopamine in reinforcement learning, how the patterns of dopamine release that are critical to the acquisition, performance, and extinction of conditioned responses are generated is poorly resolved. Here, we demonstrate that the coordinated actions of two ion channels, Kv4.3 and BKCa1.1, control the pattern of dopamine release on different time scales to regulate separate phases of reinforced behavior in mice. Inactivation of Kv4.3 in VTA dopamine neurons increases pacemaker activity and excitability that is associated with increased ramping prior to lever press in a learned instrumental response paradigm. Loss of Kv4.3 enhanced performance of the learned response and facilitated extinction. In contrast, loss of BKCa1.1 increased burst firing and phasic dopamine release that enhanced learning of an instrumental response. Inactivation of BKCa1.1 increased the reward prediction error that was associated with an enhanced extinction burst in early extinction training. These data demonstrate that temporally distinct patterns of dopamine release are regulated by the intrinsic properties of the cell to shape behavior.One sentence summary We show that ion channels in midbrain dopamine neurons are critical for patterning neurotransmitter release to regulate reinforcement learning.Competing Interest StatementThe authors have declared no competing interest. ER -