Computational models of dopamine release measured by fast scan cyclic voltammetry in vivo

Dopamine neurotransmission in the striatum is central to many normal and disease functions. Ventral midbrain dopamine neurons exhibit ongoing tonic firing that produces low extrasynaptic levels of dopamine below the detection of conventional extrasynaptic cyclic voltammetry (similar to 10-20 nanomolar), with superimposed bursts that can saturate the dopamine uptake transporter and produce transient micromolar concentrations. The bursts are known to lead to marked presynaptic plasticity via multiple mechanisms, but analysis methods for these kinetic parameters are limited. To provide a deeper understanding of the mechanics of the modulation of dopamine neurotransmission by physiological, genetic, and pharmacological means, we present three computational models of dopamine release with different levels of spatiotemporal complexity to analyze in vivo fast-scan cyclic voltammetry recordings from the dorsal striatum of mice. The models accurately fit to cyclic voltammetry data and provide estimates of presynaptic dopamine facilitation/depression kinetics and dopamine transporter reuptake kinetics, and we used the models to analyze the role of synuclein proteins in neurotransmission. The models' results support recent findings linking the presynaptic protein alpha-synuclein to the short-term facilitation and long-term depression of dopamine release, as well as reveal a new role for beta-synuclein and/or gamma-synuclein in the long-term regulation of dopamine reuptake.

Automated summary

Dopamine neurotransmission in the striatum plays a crucial role in normal and disease functions. This study utilizes computational models to analyze fast-scan cyclic voltammetry recordings in mice and provides insight into the modulation of dopamine release and reuptake. The findings support previous research and reveal the involvement of synuclein proteins in dopamine neurotransmission.