Nigrotectal Stimulation Stops Interval Timing in Mice

• Published in: Current biology 2017-12, Vol.27 (24), p.3763-3770.e3
• Main Authors: Toda, Koji, Lusk, Nicholas A., Watson, Glenn D.R., Kim, Namsoo, Lu, Dongye, Li, Haofang E., Meck, Warren H., Yin, Henry H.
• Format: Article
• Language: English
• Subjects: Animals; basal ganglia; Basal Ganglia - physiology; Behavior, Animal; Channelrhodopsins - metabolism; Female; GABAergic Neurons - physiology; interval timing; licking; Male; Mice; Optogenetics; orofacial movement; Pars Reticulata - physiology; substantia nigra pars reticulata; superior colliculus; Time Perception
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2017.11.003

Considerable evidence implicates the basal ganglia in interval timing, yet the underlying mechanisms remain poorly understood. Using a novel behavioral task, we demonstrate that head-fixed mice can be trained to show the key features of timing behavior within a few sessions. Single-trial analysis of licking behavior reveals stepping dynamics with variable onset times, which is responsible for the canonical Gaussian distribution of timing behavior. Moreover, the duration of licking bouts decreased as mice became sated, showing a strong motivational modulation of licking bout initiation and termination. Using optogenetics, we examined the role of the basal ganglia output in interval timing. We stimulated a pathway important for licking behavior, the GABAergic output projections from the substantia nigra pars reticulata to the deep layers of the superior colliculus. We found that stimulation of this pathway not only cancelled licking but also delayed the initiation of anticipatory licking for the next interval in a frequency-dependent manner. By combining quantitative behavioral analysis with optogenetics in the head-fixed setup, we established a new approach for studying the neural basis of interval timing. •Novel head-fixed timing task allows rapid acquisition of timing behavior•Single-trial analysis reveals stepping dynamics and strong motivational modulation•Nigrotectal pathway activation delays timing of future behavior Toda et al. design a novel paradigm to study interval timing in mice. Using optogenetic manipulations, the authors show that activation of the nigrotectal pathway not only suppresses ongoing behavior but also delays timing of future behavior. These results suggest that disrupting basal ganglia output can stop central networks underlying timing.