Invariant phase structure of olivo-cerebellar oscillations and its putative role in temporal pattern generation

Abstract

Complex movements require accurate temporal coordination between their components. The temporal acuity of such coordination has been attributed to an internal clock signal provided by inferior olivary oscillations. However, a clock signal can produce only time intervals that are multiples of the cycle duration. Because olivary oscillations are in the range of 5-10 Hz, they can support intervals of Ϸ100 -200 ms, significantly longer than intervals suggested by behavioral studies. Here, we provide evidence that by generating nonzero-phase differences, olivary oscillations can support intervals shorter than the cycle period. Chronically implanted multielectrode arrays were used to monitor the activity of the cerebellar cortex in freely moving rats. Harmaline was administered to accentuate the oscillatory properties of the inferior olive. Olivaryinduced oscillations were observed on most electrodes with a similar frequency. Most importantly, oscillations in different recording sites retained a constant phase difference that assumed a variety of values in the range of 0 -180°, and were maintained across large global changes in the oscillation frequency. The inferior olive may thus underlie not only rhythmic activity and synchronization, but also temporal patterns that require intervals shorter than the cycle duration. The maintenance of phase differences across frequency changes enables the olivo-cerebellar system to replay temporal patterns at different rates without distortion, allowing the execution of tasks at different speeds. cerebellar cortex ͉ harmaline ͉ inferior olive ͉ multielectrode arrays C erebellar involvement in timing is well-established, with evidence encompassing both normal and pathological conditions. Motor coordination in the 7-9 Hz range has been shown to involve the cerebellum (1), and pathologies associated with the cerebellum can either disrupt motor timing (2-4) or exaggerate tremor in this frequency range (5). The cerebellum also plays a pivotal role in timing of sensory and cognitive functions (6-11). The olivocerebellar system thus seems to be crucial for accurate timing in the range of tens to hundreds milliseconds. Two mechanisms have been proposed for cerebellar timing. First, parallel fibers have been suggested to activate Purkinje cells (PCs) with accurate delays (12-14) subserving timing. Second, oscillations in the inferior olive (IO) (15-18) have been proposed to act as a clock signal for timing. Both these mechanisms fail to cover the required range of 10-500 ms, the former because the length of a parallel fiber is exhausted within Ϸ10 ms and therefore can only support shorter time scales, and the latter because an olivary clock signal can only support temporal coordination at multiples of the clock cycle (Ϸ100-200 ms) (19). Time intervals shorter than the cycle duration could be generated by creating phase differences between different subgroups of IO neurons. Although in vitro studies demonstrate that IO oscillations can exhibit rich spatiotemporal dynamics (20, 21), the possi...

The Errors of Our Ways: Understanding Error Representations in Cerebellar-Dependent Motor Learning

“…Several solutions have been proposed on how the population complex spike activity can provide a much finer temporal resolution than individual Purkinje cells. One solution relies on the observation of non-zero phase lags among the complex spike discharge of Purkinje cells in different regions of the cerebellar cortex to generate time intervals shorter than the normal periodicity of inferior olivary neurons [102]. However, support for this concept has only been obtained after administration of harmaline.…”

Linking oscillations in cerebellar circuits

“…IO rhythmicity could definitely contribute to the organization of network activity in the cerebellar cortex (Jacobson et al, 2008; Llinás, 2009). Recent models suggest that this network may be capable of influencing PCs at a much finer temporal resolution than 10 Hz (Jacobson et al, 2008, 2009). Their model posits that GABAergic input from the DCN, which decouples IO cells by acting on gap junctions (Lang et al, 1996), would set cells out of phase from each other.…”

Dynamics of the Inferior Olive Oscillator and Cerebellar Function

“…In another case (Devor and Yarom 2002b), patches of spontaneous or stimulus-evoked STOs were observed within which the oscillations were not spatially stationary but instead propagated rapidly in a wave-like manner throughout the local network resulting in the establishment of phase differences between cells. In agreement with this, in vivo multi-electrode array recordings of Purkinje cell complex spike activity in awake rats (Jacobson et al 2009) suggest that, rather than being exactly in phase, stable phase differences can exist between neurons which oscillate at the same frequency. A networked compartmental model of olivary neurons (Schweighofer et al 1999) demonstrated that these phase differences can be achieved by variations in coupling strength between the oscillating neurons.…”

“…A recent study suggests that even asynchronous climbing fibers fire at fixed time intervals with respect to each other (Jacobson et al 2009) which is proposed to reflect fixed phase offsets between olivary neurons oscillating at the same frequency. Synchrony results from a combination of the electrotonic coupling between IO cells (Blenkinsop and Lang 2006), the subthreshold oscillations themselves (Lang et al 1997), the branching of a single olivary axon into multiple climbing fibers (Lang et al 2006a), and shared excitatory synaptic input between neighboring olivary neurons (Kistler et al 2002).…”