Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling.

Sotelo, Constantino; Llinás, Rodolfó R.; Baker, R.

doi:10.1152/jn.1974.37.3.541

Cited by 455 publications

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“…The ability to generate synchronous activity has long been ascribed to the electrotonic coupling of IO neurons by gap junctions (Llinás 1974;Llinás et al 1974). Consistent with this idea, morphological and physiological evidence of this coupling has been obtained (Benardo and Foster 1986;Llinás andYarom 1981, 1986;Sotelo et al 1974). 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).…”

Section: Significance Of Uniform Olivocerebellar Conduction Time For mentioning

confidence: 84%

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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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Section: Significance Of Uniform Olivocerebellar Conduction Time For mentioning

confidence: 84%

“…Inferior 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).…”

Section: Introductionmentioning

confidence: 99%

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

Lang¹,

Rosenbluth

2003

Journal of Neurophysiology

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“…Subsequently, gap junctions were found to couple IO neurons electrotonically, leading to the hypothesis that synchronous CS activity was attributable to this coupling Sotelo et al, 1974). Since then, the patterns of synchronous CS activity have been characterized in detail Sasaki et al, 1989;Sugihara et al, 1993;Lang et al, 1999).…”

Section: Gap Junction Coupling Between Io Neurons Mediates Cs Synchronymentioning

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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“…Substantial work has suggested that specific bandwidths of brain rhythm are underlain by electrical synapses that may permit continuous STOs among neuronal ensembles (Whittington and Traub, 2003;Hestrin and Galarreta, 2005;Sohl et al, 2005). Recently, the issue has been studied intensively in the inferior olive (IO) (Long et al, 2002;DeZeeuw et al, 2003;Placantonakis et al, 2004a,b;Leznik and Llinás, 2005), a precerebellar structure that expresses the highest density of electrical synapses in adult brain Sotelo et al, 1974) and in which neurons maintained in vitro show continuous STOs (Benardo and Foster, 1986;Llinás and Yarom, 1986). The fundamental basis of IO activity is significant both as a unique model of synaptic organization and because of its important role in movement Welsh et al, 1995;Welsh and Llinás, 1997).…”

Section: Introductionmentioning

confidence: 99%

Continuous Electrical Oscillations Emerge from a Coupled Network: A Study of the Inferior Olive using Lentiviral Knockdown of Connexin36

Placantonakis¹,

Bukovský²,

Aicher³

et al. 2006

J. Neurosci.

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Do continuous subthreshold oscillations in membrane potential within an electrically coupled network depend on gap junctional coupling? For the inferior olive (IO), modeling and developmental studies suggested that the answer is yes, although physiological studies of connexin36 knock-out mice lacking electrical coupling suggested that the answer is no. Here we addressed the question differently by using a lentivirus-based vector to express, in the IO of adult rats, a single amino acid mutation of connexin36 that disrupts the intracellular trafficking of wild-type connexin36 and blocks gap junctional coupling. Confocal microscopy of green fluorescence protein-labeled dendrites revealed that the mutant connexin36 prevented wild-type connexin36 from being expressed in dendritic spines of IO neurons. Intracellular recordings from lentivirally transduced IO networks revealed that robust and continuous subthreshold oscillations require gap junctional coupling of IO neuron somata within 40 m of one another. Topological studies indicated that the minimal coupled network for supporting such oscillations may be confined to the dendritic arbor of a single IO neuron. Occasionally, genetically uncoupled IO neurons showed transient oscillations; however, these were not sustained longer than 3 s and were 69% slower and 71% smaller than the oscillations of normal IO neurons, a finding replicated with carbenoxolone, a pharmacological antagonist of gap junctions. The experiments provided the first direct evidence that gap junctional coupling between neurons, specifically mediated by connexin36, allows a continuous network oscillation to emerge from a population of weak and episodic single-cell oscillators. The findings are discussed in the context of the importance of gap junctions for cerebellar rhythms involved in movement.

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Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling.

Cited by 455 publications

References 0 publications

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

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

Continuous Electrical Oscillations Emerge from a Coupled Network: A Study of the Inferior Olive using Lentiviral Knockdown of Connexin36

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