Dopamine Accumulation Dynamics Control Time Perception

ABSTRACT Accurate timing is fundamental to perception and behavior, and the dopaminergic system plays a key role. According to the dopamine clock hypothesis, elevated dopamine accelerates the interval clock, while reduced levels slow it. However, optogenetic activation of substantia nigra pars compacta (SNc) dopaminergic neurons paradoxically disrupts this model, suggesting greater complexity. To resolve this paradox, we monitored ventral tegmental area (VTA) dopamine activity in mice performing a time perception task. We observed a ramping-to-threshold pattern, where slower ramping corresponded to longer durations. Optogenetic activation accelerated time estimation, whereas inhibition prolonged it. Systemic dopamine elevation had no effect, but reuptake inhibition accelerated timing. Strikingly, prolonged high dopamine levels slowed time estimation, correlating with slower accumulation due to increased reuptake. Our findings challenge the dopamine clock hypothesis, demonstrating that time perception depends not on absolute dopamine levels but on their temporal accumulation dynamics. This revised framework reconciles previous contradictions and highlights the role of dopamine accumulation rates in temporal cognition.