The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN) that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs). There are two excitatory inputs to DN, mossy fiber and climbing fiber collaterals, but neither of them appears to have sufficient strength for generation of burst activity in DN. Therefore, we can assume two possible mechanisms: post-inhibitory rebound excitation and disinhibition. If rebound excitation works, phasic excitation of PCs and a concomitant inhibition of DN cells should precede the excitation of DN cells. On the other hand, if disinhibition plays a primary role, phasic suppression of PCs and activation of DN cells should be observed at the same timing. To examine these two hypotheses, we compared the activity patterns of PCs in the cerebrocerebellum and DN cells during step-tracking wrist movements in three Japanese monkeys. As a result, we found that the majority of wrist-movement-related PCs were suppressed prior to movement onset and the majority of wrist-movement-related DN cells showed concurrent burst activity without prior suppression. In a minority of PCs and DN cells, movement-related increases and decreases in activity, respectively, developed later. These activity patterns suggest that the initial burst activity in DN cells is generated by reduced inhibition from PCs, i.e., by disinhibition. Our results indicate that suppression of PCs, which has been considered secondary to facilitation, plays the primary role in generating outputs from DN. Our findings provide a new perspective on the mechanisms used by PCs to influence limb motor control and on the plastic changes that underlie motor learning in the cerebrocerebellum.

A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e., mossy fibers (MFs), Golgi cells (GoCs), and Purkinje cells (PCs), in three monkeys performing wrist movements in two different forearm postures. The results revealed distinct steps of information processing. First, MF activities displayed temporal and directional properties that were remarkably similar to those of M1/PM neurons, suggesting that MFs relay near copies of outputs from these motor areas. Second, all GoCs had a stereotyped pattern of activity independent of movement direction or forearm posture. Instead, GoC activity resembled an average of all MF activities. Therefore, inhibitory GoCs appear to provide a filtering function that passes only prominently modulated MF inputs to granule cells. Third, PCs displayed highly complex spatiotemporal patterns of activity, with coordinate frames distinct from those of MF inputs and directional tuning that changed abruptly before movement onset. The complexity of PC activities may reflect rapidly changing properties of the peripheral motor apparatus during movement. Overall, the cerebellar cortex appears to transform a representation of outputs from M1/PM into different movement representations in a posture-dependent manner and could work as part of a forward model that predicts the state of the peripheral motor apparatus.

To examine whether mossy fibers (MFs) in the cerebellar hemisphere show delay activity, we recorded MF activity during a wrist movement task with a random instructed delay period in two monkeys. Among 155 task-related MFs, 70 MFs (45%) demonstrated significant delay activity. Those MFs were widely distributed in the cerebellar hemisphere. Some of the activities were evoked by instruction cue presentation, whereas other activity started in anticipation of the upcoming go signal. For most MFs, the delay activities showed directional tuning. These patterns of the activity were in common with those of neurons in the cerebral motor cortices.

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An accurate estimate of elapsed time is essential for anticipating the timing of future events. Here, we show that the ability to estimate elapsed time on a reaction time (RT) task improved with training during which human participants learned to anticipate the onset of a "Go" signal. In each trial, a warning signal preceded the Go signal by a temporal interval (i.e., foreperiod). The duration of the foreperiod was randomly drawn from a rectangular distribution (1-2 s). Participants were required to initiate a response immediately after the Go signal and performed the task for 480 trials/day for 12 days. Anticipation should have been governed by the probability that the Go signal would occur (hazard rate), which increased for longer foreperiods. Indeed, RTs decreased for longer foreperiods and were inversely related to the hazard rate. The pattern of RT decrease was well explained by the subjective hazard rate, which was formalized based on the assumption that the uncertainty of estimates of elapsed time scales with time (Weber's law). Notably, RTs demonstrated a more linear decrease as a function of foreperiod in LATE compared with EARLY training sessions. This involved a decrease in the Weber fraction used in the subjective hazard rate. The results indicate that the uncertainty associated with estimating elapsed time was reduced as participants learned and used the hazard rate to anticipate the onset of the Go signal. This finding suggests that the ability to estimate elapsed time improves with training on behavioral tasks that implicitly engage timing mechanisms.