Serotonin Modulation of Inferior Olivary Oscillations and Synchronicity: A Multiple‐electrode Study in the Rat Cerebellum

Sugihara, Izumi; Lang, Eric J.; Llinás, Rodolfó R.

doi:10.1111/j.1460-9568.1995.tb00657.x

Cited by 138 publications

(91 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: 77%

“…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: 94%

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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: 77%

Section: Resultsmentioning

confidence: 94%

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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“…However, Maura et al (1988) have shown that endogenous release of glutamate in the cerebellum was inhibited by the 5-HT 2 receptor agonist DOI, which was reversed by the selective 5-HT 2 receptor antagonist ketanserin. Through the use of 5-HT and various agonists and antagonists, the expression of 5-HT 2A R has also been demonstrated in Purkinje cells (Sugihara et al 1995), which is in agreement with the staining results with our MAb. We do not presently know the reason for this discrepancy.…”

Section: Discussionsupporting

confidence: 76%

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

Yoder

Shih

et al. 1998

J Histochem Cytochem.

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SUMMARY Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT 2A receptor. To generate MAbs against 5-HT 2A R, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT 2A R recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT 2A R, rat and human brain lysate, and lysate from cell lines transfected with 5-HT 2A R cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT 2A R N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT 2A R in lysates from rat brain and a 5-HT 2A R-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT 2A R but not with recombinant 5-HT 2B R and 5-HT 2C R. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies. (J Histochem Cytochem 46:811-824, 1998)

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“…Autocorrelation and cross-correlation histograms with a time bin of 1 msec were plotted for SS firing from single and paired PCs, respectively. The strength of the oscillation was quantified with a rhythm index (RI) introduced by Sugihara et al (1995). Briefly, peaks and valleys were recognized if their heights and depths exceeded the mean baseline level Ϯ SD (measured at time lags of 250 -300 msec).…”

Section: Methodsmentioning

confidence: 99%

Inactivation of Calcium-Binding Protein Genes Induces 160 Hz Oscillations in the Cerebellar Cortex of Alert Mice

Chéron¹,

Gall²,

Servais³

et al. 2004

J. Neurosci.

108

102

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Oscillations in neuronal populations may either be imposed by intrinsically oscillating pacemakers neurons or emerge from specific attributes of a distributed network of connected neurons. Calretinin and calbindin are two calcium-binding proteins involved in the shaping of intraneuronal Ca 2ϩ fluxes. However, although their physiological function has been studied extensively at the level of a single neuron, little is known about their role at the network level. Here we found that null mutations of genes encoding calretinin or calbindin induce 160 Hz local field potential oscillations in the cerebellar cortex of alert mice. These oscillations reached maximum amplitude just beneath the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked to the oscillations and synchronized along the parallel fiber axis. The oscillations reversibly disappeared when gap junctions or either GABA A or NMDA receptors were blocked. Cutaneous stimulation of the whisker region transiently suppressed the oscillations. However, the intrinsic somatic excitability of Purkinje cells recorded in slice preparation was not significantly altered in mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges from a network mechanism combining synchronization of Purkinje cell assemblies through parallel fiber excitation and the network of coupled interneurons of the molecular layer. These findings demonstrate that subtle genetically induced modifications of Ca 2ϩ homeostasis in specific neuron types can alter the observed dynamics of the global network.

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Serotonin Modulation of Inferior Olivary Oscillations and Synchronicity: A Multiple‐electrode Study in the Rat Cerebellum

Cited by 138 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

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor

Inactivation of Calcium-Binding Protein Genes Induces 160 Hz Oscillations in the Cerebellar Cortex of Alert Mice

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Serotonin Modulation of Inferior Olivary Oscillations and Synchronicity: A Multiple‐electrode Study in the Rat Cerebellum

Cited by 138 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

Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT2AReceptor

Inactivation of Calcium-Binding Protein Genes Induces 160 Hz Oscillations in the Cerebellar Cortex of Alert Mice

Contact Info

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Development and Characterization of Monoclonal Antibodies Specific to the Serotonin 5-HT_2AReceptor