Organization of Olivocerebellar Activity in the Absence of Excitatory Glutamatergic Input

Lang, Eric J.

doi:10.1523/jneurosci.21-05-01663.2001

Cited by 85 publications

(98 citation statements)

References 47 publications

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“…Previous work on CSs in the cerebellar cortex has described zero-phase synchrony between PC pairs (26)(27)(28)(29). Our study extends these results to stable, nonzero-phase differences.…”

Section: Discussionsupporting

confidence: 82%

“…In this experiment, oscillation frequency was Ϸ8.6 Hz on all 15 electrodes that exhibit oscillatory activity. Across experiments (n ϭ 13), stable oscillation frequency was in the range of 4-11 Hz with 1 exception (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Within each experiment, oscillation frequency was similar across electrodes, and occasional epochs of frequency deviation ( Fig.…”

Section: Resultsmentioning

confidence: 89%

See 1 more Smart Citation

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

Jacobson

Lev

Yarom

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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...

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“…Previous work on CSs in the cerebellar cortex has described zero-phase synchrony between PC pairs (26)(27)(28)(29). Our study extends these results to stable, nonzero-phase differences.…”

Section: Discussionsupporting

confidence: 82%

Section: Resultsmentioning

confidence: 89%

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

Jacobson

Lev

Yarom

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In fact, the density of neuronal gap junctions in the IO is one of the highest in the CNS (Belluardo et al 2000;Condorelli et al 1998;De Zeeuw et al 1995). Moreover, synchronous CS activity remains following block of excitatory and/or inhibitory input to the IO (Lang 2001(Lang , 2002, which, given the virtual lack of local chemical synaptic interactions between IO neurons, further implicates gap junction coupling as the origin of CS synchrony.…”

Section: Significance Of Uniform Olivocerebellar Conduction Time For mentioning

confidence: 99%

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Lang¹,

Rosenbluth

2003

Journal of Neurophysiology

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Lang, Eric J. and Jack Rosenbluth. Role of myelination in the development of a uniform olivocerebellar conduction time. J Neurophysiol 89: 2259 -2270, 2003. First published December 18, 2002 10.1152/jn.00922.2002. Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at Ϸ4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony. I N T R O D U C T I O NInferior olivary (IO) neurons are electrotonically coupled via numerous gap junctions (Llinás and Yarom 1981;Llinás et al. 1974;Sotelo et al. 1974). Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al. 2000;Condorelli et al. 1998;De Zeeuw et al. 1995). This coupling allows IO neurons to generate precisely (on a millisecond time scale) synchronized activity that results in simultaneous complex spike (CS) activity in the cerebellum (Lang et al. 1999;Sasaki et al. 1989;Sugihara et al. 1993;Yamamoto et al. 2001).Maintenance of the synchronization present in IO discharges presents a challenge for the olivocerebellar system because the length of the olivocerebellar pathway to different points on the cerebellar cortex varies. In rats, there can be more than a twofold difference in the length of the olivocerebellar projection to different regions of the cortex (Sugihara et al. 1993). To preserve the precise synchronization present at...

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“…Synchronous CS activity remains after block of major synaptic input to the IO, suggesting IO afferent activity is in fact not needed (Lang et al, 1996;Lang, 2001Lang, , 2002; subthreshold oscillations have never been reported in vivo (Crill and Kennedy, 1967;Crill, 1970;Llinás et al, 1974;Ruigrok and De Zeeuw, 1993;Ruigrok and Voogd, 1995); and autocorrelograms of rhythmic CS activity are not consistent with it arising from subthreshold oscillations (E. J. Lang, unpublished observations).…”

Section: Introductionmentioning

confidence: 99%

Block of Inferior Olive Gap Junctional Coupling Decreases Purkinje Cell Complex Spike Synchrony and Rhythmicity

2006

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Inferior olivary (IO) neurons are electrotonically coupled by gap junctions. This coupling is thought to underlie synchronous complex spike (CS) activity generated by the olivocerebellar system in Purkinje cells, and also has been hypothesized to be necessary for IO neurons to generate spontaneous oscillatory activity. These characteristics of olivocerebellar activity have been proposed to be central to the role of this system in motor coordination. However, the relationship of gap junction coupling between IO neurons to synchronous and rhythmic CS activity has never been directly tested. Thus, to address this issue, multiple electrode recordings were obtained from crus 2a Purkinje cells, and carbenoxolone, a gap junction blocker, was injected into the IO. Carbenoxolone reduced CS synchrony by 50% overall, but in some experiments, Ͼ80% reductions were achieved. Carbenoxolone also reduced the average firing rate by 50%, suggesting that electrical coupling is a significant source of excitation for IO neurons. Moreover, carbenoxolone caused a reduction in the ϳ10 Hz rhythmicity of CS activity, and this reduction was correlated with the extent to which the injection reduced CS synchrony. Lastly, carbenoxolone was found to reverse or prevent changes in synchrony that are normally induced by injection of GABA A and glutamate receptor antagonists into the IO, suggesting that the effects of these drugs on CS synchrony patterns require electrical coupling of IO neurons. In sum, our results provide direct evidence that electrical coupling of IO neurons underlies synchronous CS activity, and suggest important roles for this coupling in shaping other aspects of IO spiking patterns.

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Organization of Olivocerebellar Activity in the Absence of Excitatory Glutamatergic Input

Cited by 85 publications

References 47 publications

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

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

Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Block of Inferior Olive Gap Junctional Coupling Decreases Purkinje Cell Complex Spike Synchrony and Rhythmicity

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