Temporal scaling of dopamine neuron firing and dopamine release by distinct ion channels shape behavior

Abstract

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.

Distinct dynamics and intrinsic properties in ventral tegmental area populations mediate reward association and motivation

“…In addition to heterogeneous afferent and efferent connectivity, distinct dopamine projection populations have distinct electrophysiological properties (Lammel et al, 2008;Lammel et al, 2011;Poulin et al, 2018;Heymann et al, 2020), and ion channel expression patterns (Juarez et al, 2023;Simon et al, 2023), factors that likely contribute to their distinct functional properties. However, it remains unclear how information about reward-related stimuli and motivation during reward-seeking behaviors is encoded across specific VTA subpopulations and whether distinct intrinsic neurophysiological and circuit connectivity properties define these populations.…”