Midbrain Dopamine Warps Subjective Time via Threshold Setting But Not Clock Speed

Abstract

Interval timing is an evolutionarily well-preserved function that presents similar behavioral signatures across different species. However, the neural basis of interval timing remains an open question. For instance, although dopamine has been implicated as a vital component of the internal clock, its precise role is debated due to equivocal findings from various methodologies and their interpretations. We tested this question by optogenetically exciting versus inhibiting tyrosine hydroxylase-positive (TH+) neurons of the substantia nigra pars compacta while male mice produced at least a 3-s-long interval by depressing a lever for reward. Excitation of TH+ neurons shifted their timing behavior to the right, while inhibition led to a shift to the left. Our drift-diffusion timing model-based analysis of the behavioral data clearly showed that TH+ neuron excitation and inhibition heightened and lowered the timing threshold, respectively, without affecting the rate of temporal integration (i.e., clock speed). Our work attributes a clear mechanistic role (i.e., threshold setting) to nigrostriatal dopaminergic function as part of the internal clock.