LAUSR

Just over half a century ago Bell and Grimm (1) were the first to record simultaneously from multiple Purkinje cells, revealing that different Purkinje cells can fire in synchrony within the same few milliseconds. This held true for both the complex spikes (CSs) that are modulated by the climbing fiber system and the simple spikes (SSs) that are modulated by the mossy fiber–parallel fiber system (Fig. 1 A and B). Since climbing fibers originate from neurons in the inferior olive that are extensively coupled by gap junctions (2, 3) and tend to oscillate (4, 5), systems physiologists have focused largely on the question of what the role of CS synchrony might be. To date, several studies over the past decades have revealed that CS synchrony may contribute to the coordination of motor behavior. For example, Welsh et al. (6) have provided compelling evidence that dynamic patterning of CS synchrony may allow for different combinations of muscles to be used to facilitate the timing and sequence of movements. Indeed, synchronized patterns of CS activity may contribute not only to the initiation of relatively simple reflex movements (7, 8) but also to more complex types of behaviors that require extensive training over time (9–12). Moreover, recent studies raise the possibility that CS signaling, and thereby CS synchrony, in particular microzones, might also be involved in reward signaling following acquisition of complex behaviors (9, 13, 14). Unlike the progress in our understanding of the potential role(s) of synchronous firing of CSs, that of the SSs has been trailing behind. SS synchrony may increase with increasing CS synchrony (15), SS synchrony during movements may be greater among Purkinje cells that process the same type of signals (e.g., horizontal versus vertical eye movement signals) (15), and SS synchrony of Purkinje cells receiving input from the same parallel fiber beam may be correlated with certain movement epochs (16), but so far SS synchrony of single-unit Purkinje cells has not been directly correlated with any specific kinematic parameter. This long-standing lack of a novel concept backed up with empirical evidence is now provided by SedaghatNejad et al. (17) in PNAS. They show that SS synchrony of Purkinje cells in the oculomotor vermis of marmosets can be associated with the end of targeted or spontaneous saccadic eye movements in that it peaks at the onset of deceleration. Importantly, this correlation cannot be biased by an increase in SS firing rate, because it actually drops. As such, the increase in synchrony of SSs diverges from that of CSs, which usually increases when the firing rate increases (7, 8). The probability for SS synchronization was greatest for saccades that were in the opposite direction of that for optimal CS modulation, elucidating the general association between SS synchrony and CS synchrony uncovered previously (15). Inspired by the concept that SS synchrony may facilitate the timing of deceleration of movements, one can now go back to previously published datasets of Purkinje cell pairs related to other types of behaviors relevant for other species. For example, Romano et al. (18, 19) have recorded from Purkinje cell pairs in crus I and II during whisker movements in mice. In these datasets, one can observe a relation not only between CS synchrony and movement onset (Fig. 1C) but indeed also between SS synchrony and movement deceleration (Fig. 1D). Thus, the discovery by Sedaghat-Nejad et al. (17) may generalize across cerebellar lobules, types of behavior, and species. How may SS synchrony exert its effects downstream in the cerebellar nuclei? Given that the synchrony is maximal during SS suppression (17), it may well exert its effects when the cerebellar nuclei neurons are disinhibited by reduced inhibitory input from the GABAergic Purkinje cells. Due to the modest Purkinje-to-nuclear convergence ratio and fast inhibitory postsynaptic current kinetics, the increased SS synchrony could result in a reaction of burst activity, made of spikes with very precise timing at the millisecond scale (20), via which premotor processes in the brainstem can be fine-tuned at a high temporal resolution (Fig. 1A). In other words, cerebellar nuclei neurons may be particularly sensitive for the level of SS synchrony during SS suppression and thereby able to control the timing of deceleration of movements. As highlighted in the paper by Sedaghat-Nejad et al. (17), this aligns indeed well with the profound impact of cerebellar cortical lesions on the termination of movements, including that of saccades (21). By highlighting their concept on SS synchrony, SedaghatNejad et al. (17) have opened up an avenue of new interesting research lines and corresponding questions. For example, their findings raise the intriguing possibility that whereas synchrony of CSs could facilitate the movement initiation, that of SSs may determine movement cessation (Fig. 1 B–D). Given that SS synchrony was highest between Purkinje cell pairs that showed optimal CS modulation around the same axis in space (albeit in opposite direction as the SS modulation), it appears likely that the start and end of a movement are efficiently coordinated within the same upbound or downbound module controlling particular muscle pairs (22). Likewise, the findings of Sedaghat-Nejad et al. (17) raise interesting questions about the relation between