Integrator dynamics in the cortico-basal ganglia loop for flexible motor timing.

Flexible control of motor timing is crucial for behaviour1-4. Before volitional movement begins, the frontal cortex and striatum exhibit ramping spiking activity, with variable ramp slopes anticipating movement onsets5-12. This activity in the cortico-basal ganglia loop may function as an adjustable 'timer,' triggering actions at the desired timing. However, because the frontal cortex and striatum share similar ramping dynamics and are both necessary for timing behaviours, distinguishing their individual roles in this timer function remains challenging. Here, to address this, we conducted perturbation experiments combined with multi-regional electrophysiology in mice performing a flexible lick-timing task. Following transient silencing of the frontal cortex, cortical and striatal activity swiftly returned to pre-silencing levels and resumed ramping, leading to a shift in lick timing close to the silencing duration. Conversely, briefly inhibiting the striatum caused a gradual decrease in ramping activity in both regions, with ramping resuming from post-inhibition levels, shifting lick timing beyond the inhibition duration. Thus, inhibiting the frontal cortex and striatum effectively paused and rewound the timer, respectively. These findings are consistent with a model in which the striatum is part of a network that temporally integrates input from the frontal cortex and generates ramping activity that regulates motor timing.